@article {pmid38672774,
year = {2024},
author = {Wani, I and Koppula, S and Balda, A and Thekkekkara, D and Jamadagni, A and Walse, P and Manjula, SN and Kopalli, SR},
title = {An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {38672774},
issn = {2075-1729},
abstract = {Neuroinflammation is the major cause of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Currently available drugs present relatively low efficacy and are not capable of modifying the course of the disease or delaying its progression. Identifying well-tolerated and brain-penetrant agents of plant origin could fulfil the pressing need for novel treatment techniques for neuroinflammation. Attention has been drawn to a large family of flavonoids in citrus fruits, which may function as strong nutraceuticals in slowing down the development and progression of neuroinflammation. This review is aimed at elucidating and summarizing the effects of the flavonoid tangeretin (TAN) in the management of neuroinflammation-mediated neurodegenerative disorders. A literature survey was performed using various resources, including ScienceDirect, PubMed, Google Scholar, Springer, and Web of Science. The data revealed that TAN exhibited immense neuroprotective effects in addition to its anti-oxidant, anti-diabetic, and peroxisome proliferator-activated receptor-γ agonistic effects. The effects of TAN are mainly mediated through the inhibition of oxidative and inflammatory pathways via regulating multiple signaling pathways, including c-Jun N-terminal kinase, phosphoinositide 3-kinase, mitogen-activated protein kinase, nuclear factor erythroid-2-related factor 2, extracellular-signal-regulated kinase, and CRE-dependent transcription. In conclusion, the citrus flavonoid TAN has the potential to prevent neuronal death mediated by neuroinflammatory pathways and can be developed as an auxiliary therapeutic agent in the management of neurodegenerative disorders.},
}

@article {pmid38671987,
year = {2024},
author = {Lal, U and Chikkankod, AV and Longo, L},
title = {A Comparative Study on Feature Extraction Techniques for the Discrimination of Frontotemporal Dementia and Alzheimer's Disease with Electroencephalography in Resting-State Adults.},
journal = {Brain sciences},
volume = {14},
number = {4},
pages = {},
pmid = {38671987},
issn = {2076-3425},
abstract = {Early-stage Alzheimer's disease (AD) and frontotemporal dementia (FTD) share similar symptoms, complicating their diagnosis and the development of specific treatment strategies. Our study evaluated multiple feature extraction techniques for identifying AD and FTD biomarkers from electroencephalographic (EEG) signals. We developed an optimised machine learning architecture that integrates sliding windowing, feature extraction, and supervised learning to distinguish between AD and FTD patients, as well as from healthy controls (HCs). Our model, with a 90% overlap for sliding windowing, SVD entropy for feature extraction, and K-Nearest Neighbors (KNN) for supervised learning, achieved a mean F1-score and accuracy of 93% and 91%, 92.5% and 93%, and 91.5% and 91% for discriminating AD and HC, FTD and HC, and AD and FTD, respectively. The feature importance array, an explainable AI feature, highlighted the brain lobes that contributed to identifying and distinguishing AD and FTD biomarkers. This research introduces a novel framework for detecting and discriminating AD and FTD using EEG signals, addressing the need for accurate early-stage diagnostics. Furthermore, a comparative evaluation of sliding windowing, multiple feature extraction, and machine learning methods on AD/FTD detection and discrimination is documented.},
}

@article {pmid38670598,
year = {2024},
author = {Yang, A and Yi, X and Zhang, H and Shen, R and Kou, X},
title = {Diosmetin derivatives as multifunctional anti-AD ligands: Design, synthesis, and biological evaluation.},
journal = {Chemical biology & drug design},
volume = {103},
number = {4},
pages = {e14529},
doi = {10.1111/cbdd.14529},
pmid = {38670598},
issn = {1747-0285},
mesh = {*Cholinesterase Inhibitors/pharmacology/chemical synthesis/chemistry/metabolism ; *Acetylcholinesterase/metabolism ; Animals ; *Butyrylcholinesterase/metabolism ; *Alzheimer Disease/drug therapy/metabolism ; *Amyloid beta-Peptides/metabolism/antagonists & inhibitors ; *Drug Design ; *Caenorhabditis elegans/drug effects/metabolism ; *Molecular Docking Simulation ; Ligands ; *Blood-Brain Barrier/metabolism ; Humans ; *Reactive Oxygen Species/metabolism ; *Flavonoids/chemistry/pharmacology/chemical synthesis ; Antioxidants/pharmacology/chemistry/chemical synthesis ; Structure-Activity Relationship ; Protein Aggregates/drug effects ; },
abstract = {With the increasing aging population, rational design of drugs for Alzheimer's disease (AD) treatment has become an important research area. Based on the multifunctional design strategy, four diosmetin derivatives (1-4) were designed, synthesized, and characterized by [1]H NMR, [13]C NMR, and MS. Docking study was firstly applied to substantiate the design strategies and then the biological activities including cholinesterase inhibition, metal chelation, antioxidation and β-amyloid (Aβ) aggregation inhibition in vitro were evaluated. The results showed that 1-4 had good acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition, metal chelation (selective chelation of Cu[2+] ions), antioxidation, self-induced, Cu[2+]-induced, and AChE-induced Aβ aggregation inhibition activities, and suitable blood-brain barrier (BBB) permeability. Especially, compound 3 had the strongest inhibitory effect on AChE (10[-8] M magnitude) and BuChE (10[-7] M magnitude) and showed the best inhibition on AChE-induced Aβ aggregation with 66.14% inhibition ratio. Furthermore, compound 3 could also reduce intracellular reactive oxygen species (ROS) levels in Caenorhabditis elegans and had lower cytotoxicity. In summary, 3 might be considered as a potential multifunctional anti-AD ligand.},
}

*Cholinesterase Inhibitors/pharmacology/chemical synthesis/chemistry/metabolism
*Acetylcholinesterase/metabolism
Animals
*Butyrylcholinesterase/metabolism
*Alzheimer Disease/drug therapy/metabolism
*Amyloid beta-Peptides/metabolism/antagonists & inhibitors
*Drug Design
*Caenorhabditis elegans/drug effects/metabolism
*Molecular Docking Simulation
Ligands
*Blood-Brain Barrier/metabolism
Humans
*Reactive Oxygen Species/metabolism
*Flavonoids/chemistry/pharmacology/chemical synthesis
Antioxidants/pharmacology/chemistry/chemical synthesis
Structure-Activity Relationship
Protein Aggregates/drug effects

@article {pmid38670195,
year = {2024},
author = {Nawaz, M and Afridi, MN and Ullah, I and Khan, IA and Ishaq, MS and Su, Y and Rizwan, HM and Cheng, KW and Zhou, Q and Wang, M},
title = {The inhibitory effects of endophytic metabolites on glycated proteins under non-communicable disease conditions: A review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {131869},
doi = {10.1016/j.ijbiomac.2024.131869},
pmid = {38670195},
issn = {1879-0003},
abstract = {Protein glycation in human body is closely linked to the onset/progression of diabetes associated complications. These glycated proteins are commonly known as advanced glycation end products (AGEs). Recent literature has also highlighted the involvement of AGEs in other non-communicable diseases (NCDs) such as cardiovascular, cancer, and Alzheimer's diseases and explored the impact of plant metabolites on AGEs formation. However, the significance of endophytic metabolites against AGEs has recently garnered attention but has not been thoroughly summarized thus far. Therefore, the objective of this review is to provide a comprehensive overview of the importance of endophytic metabolites in combating AGEs under NCDs conditions. Additionally, this review aims to elucidate the processes of AGEs formation, absorption, metabolism, and their harmful effects. Collectively, endophytic metabolites play a crucial role in modulating signaling pathways and enhancing the digestibility properties of gut microbiota (GM) by targeting on AGEs/RAGE (receptor for AGEs) axis. Furthermore, these metabolites exhibit anti-AGEs activities similar to those derived from host plants, but at a lower cost and higher production rate. The use of endophytes as a source of such metabolites offers a risk-free and sustainable approach that holds substantial potential for the treatment and management of NCDs.},
}

@article {pmid38670061,
year = {2024},
author = {Queissner, R and Fellendorf, FT and Dalkner, N and Bengesser, SA and Maget, A and Birner, A and Platzer, M and Reininghaus, B and Häussl, A and Schönthaler, E and Tmava-Berisha, A and Lenger, M and Reininghaus, EZ},
title = {The influence of chronic inflammation on the illnesscourse of bipolar disorder: A longitudinal study.},
journal = {Journal of psychiatric research},
volume = {174},
number = {},
pages = {258-262},
doi = {10.1016/j.jpsychires.2024.04.024},
pmid = {38670061},
issn = {1879-1379},
abstract = {INTRODUCTION: C-reactive protein (CRP) is a systemic inflammatory marker, which indicates systemic inflammatory processes It is involved in different inflammatory processes of the body and is a reliable marker for the general inflammatory state of the body. High sensitive CRP seems to play a key role as a state and trait marker of bipolar disorder (BD). In the current study, we tried to determine the long-term effect of CRP levels on clinical symptoms and illness course of bipolar disorder.

METHODS: For the current study, we examined 106 patients with BD for a period of four years. Participants underwent a clinical screening for depressive and manic episodes with the Hamilton Depression Scale (HAMD) and the Young Mania Rating Score (YMRS) and a serological diagnostic for inflammatory parameters every six months, thus leading to 8 measurement times in total. Patients with the presence of severe medical or neurological comorbidities such as active cancer, chronic obstructive lung disease, rheumatoid arthritis, systemic lupus erythematosus, Alzheimer's disease, Parkinson's disease, Huntington's disease or multiple sclerosis and acute infections were not included in the study.

RESULTS: In our sample, 26% showed a mean hsCRP above 5 mg/dl. Those patients showed a significantly higher mean YMRS score than those with a mean hsCRP under 5 mg/dl during our observation period. Regarding HAMD there was no significant difference in hsCRP values. The existence of lithium treatment showed no significant influence on mean hsCRP levels between the start and endpoint.

CONCLUSION: Individuals who were exposed to a higher level of inflammation over time suffered from more manic symptoms in this period. These findings underline the hypothesis that inflammatory processes have an accumulative influence on the illness course of BD, especially concerning manic symptoms and episodes.},
}

@article {pmid38669966,
year = {2024},
author = {Zhao, P and Cheng, P and Wang, J and Zhu, G and Wang, X},
title = {Shenqi Yizhi prescription prevents AβO-induced memory impairment in mice by regulating the contractility of brain pericytes.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {129},
number = {},
pages = {155639},
doi = {10.1016/j.phymed.2024.155639},
pmid = {38669966},
issn = {1618-095X},
abstract = {BACKGROUND: Cerebral microcirculation disturbance manifested by decrease of cerebral blood flow (CBF) is one of early features of Alzheimer's disease (AD). Shenqi Yizhi prescription (SQYZ) is widely used in the treatment of AD. However, the effect of SQYZ on the early feature of AD is not clarified.

PURPOSE: To explore the effect and mechanism of SQYZ on AD-like behavior from the perspective of early pathological features of AD.

METHODS: The fingerprint of SQYZ was established by ultra-high-performance liquid chromatograph. The improvement effect of SQYZ on Aβ1-42 Oligomer (AβO)-induced AD-like behavior of mice was evaluated by behavioral test. The changes of CBF were detected by laser doppler meter and laser speckle imaging. The pathological changes of the hippocampus were observed by HE staining and transmission electron microscope. The expressions of intercellular communication molecules were detected by western blotting or immunofluorescence staining. The content of platelet-derived growth factor-BB (PDGF-BB) was detected by ELISA. Finally, the core components of SQYZ were docked with platelet-derived growth factor receptor beta (PDGFRβ) using AutoDock Vina software.

RESULTS: The similarity of the components in SQYZ extracted from different batches of medicinal materials was higher than 0.9. SQYZ administration could improve AβO-induced memory impairment and CBF reduction. Compared with the sham group, the number of neurons in the hippocampi of AβO group was significantly reduced, and the microvessels were shrunken and deformed. By contrary, SQYZ administration mitigated those pathological changes. Compared with the sham mice, the expressions of CD31, N-cadherin, PDGFRβ, glial fibrillary acidic protein, phosphorylation of focal adhesion kinase, integrin β1, and integrin α5 in the hippocampi of AβO mice were significantly increased. However, SQYZ administration significantly reduced AβO-induced expression of those proteins. Interestingly, the effect of PDGFRβ inhibitor, sunitinib demonstrated a consistent modulating effect as SQYZ. Finally, the brain-entering components of SQYZ, including ginsenoside Rg5, coptisine, cryptotanshinone, dihydrotanshinone IIA, stigmasterol, and tanshinone IIA had high binding force with PDGFRβ, implicating PDGFRβ as a potential target for SQYZ.

CONCLUSIONS: Our data indicate that SQYZ improves CBF in AβO-triggered AD-like mice through inhibiting brain pericyte contractility, indicating the treatment potential of SQYZ for AD at the early stage.},
}

@article {pmid38669547,
year = {2024},
author = {Elghanam, Y and Purja, S and Kim, EY},
title = {Biomarkers as Endpoints in Clinical Trials for Alzheimer's Disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-240008},
pmid = {38669547},
issn = {1875-8908},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that imposes economic and societal burden. Biomarkers have played a crucial role in the recent approval of aducanumab and lecanemab as disease-modifying therapies which marked a significant milestone for the treatment of AD. The inclusion of biomarkers in AD trials facilitates precise diagnosis, monitors safety, demonstrates target engagement, and supports disease modification.

OBJECTIVE: This study analyzed the utilization state and trends of biomarkers as endpoints in AD trials.

METHODS: In this retrospective study, trials were collected by searching clinicaltrials.gov using the term "Alzheimer". Primary and secondary outcomes were analyzed separately for each phase.

RESULTS: Among the 1,048 analyzed trials, 313 (29.87%) adopted biomarkers as primary endpoints and 364 (34.73%) as secondary endpoints, mainly in phases 1 and 2. The top three biomarkers adopted as primary endpoints in phases 1, 2, and 3 were amyloid-PET, tau-PET, and MRI. The top three biomarkers adopted as secondary endpoints, in phase 1, were cerebrospinal fluid (CSF) amyloid-β (Aβ), blood Aβ and amyloid-PET; in phase 2, they were MRI, CSF Aβ, and CSF phospho-tau; and in phase 3, they were amyloid PET, MRI, and blood Aβ. There was a statistically significant increase in the adoption of biomarkers as primary endpoints in phase 2 trials (p = 0.001) and secondary endpoints in phase 3 trials (p = 0.001).

CONCLUSIONS: The growing recognition of the importance of biomarkers in AD trial' design and drug development is evident by the significant steady increase in biomarkers' utilization in phases 2 and 3.},
}

@article {pmid38669543,
year = {2024},
author = {Miller, MR and Lariviere, L and Pagnier, GJ and Aygar, S and Wieckiewic, N and Maesako, M and Bacskai, BJ and Kastanenka, KV},
title = {NB-02 Protects Neurons and Astrocytes from Oligomeric Amyloid-β-Mediated Damage.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-231387},
pmid = {38669543},
issn = {1875-8908},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures. Pretreatment with NB-02 prevented pathological calcium elevations in neurons and astrocytes after application of toxic soluble amyloid-β (Aβ) oligomers. NB-02 also prevented cell death associated with the addition of soluble Aβ oligomers suggesting NB-02 is effective at protecting both neurons and astrocytes from Aβ-mediated damage.},
}

@article {pmid38669538,
year = {2024},
author = {Marr, C and McDowell, B and Holmes, C and Edwards, CJ and Cardwell, C and McHenry, M and Meenagh, G and Teeling, JL and McGuinness, B},
title = {The RESIST Study: Examining Cognitive Change in Rheumatoid Arthritis Patients with Mild Cognitive Impairment Being Treated with a TNF-Inhibitor Compared to a Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-231329},
pmid = {38669538},
issn = {1875-8908},
abstract = {BACKGROUND: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer's disease progression by reducing inflammation.

OBJECTIVE: To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD).

METHODS: 251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA).

RESULTS: No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = -1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = -0.4, 1.3).

CONCLUSIONS: There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention.},
}

@article {pmid38669535,
year = {2024},
author = {Thunell, JA and Joyce, GF and Ferido, PM and Chen, Y and Guadamuz, JS and Qato, DM and Zissimopoulos, JM},
title = {Diagnoses and Treatment of Behavioral and Psychological Symptoms of Dementia Among Racially and Ethnically Diverse Persons Living with Dementia.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-231266},
pmid = {38669535},
issn = {1875-8908},
abstract = {BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) and prescribed central nervous system (CNS) active drugs to treat them are prevalent among persons living with Alzheimer's disease and related dementias (PLWD) and lead to negative outcomes for PLWD and their caregivers. Yet, little is known about racial/ethnic disparities in diagnosis and use of drugs to treat BPSD.

OBJECTIVE: Quantify racial/ethnic disparities in BPSD diagnoses and CNS-active drug use among community-dwelling PLWD.

METHODS: We used a retrospective cohort of community-dwelling Medicare Fee-for-Service beneficiaries with dementia, continuously enrolled in Parts A, B and D, 2017-2019. Multivariate logistic models estimated rates of BPSD diagnosis and, conditional on diagnosis, CNS-active drug use.

RESULTS: Among PLWD, 67.1% had diagnoses of an affective, psychosis or hyperactivity symptom. White (68.3%) and Hispanic (63.9%) PLWD were most likely, Blacks (56.6%) and Asians (52.7%) least likely, to have diagnoses. Among PLWD with BPSD diagnoses, 78.6% took a CNS-active drug. Use was highest among whites (79.3%) and Hispanics (76.2%) and lowest among Blacks (70.8%) and Asians (69.3%). Racial/ethnic differences in affective disorders were pronounced, 56.8% of white PLWD diagnosed; Asians had the lowest rates (37.8%). Similar differences were found in use of antidepressants.

CONCLUSIONS: BPSD diagnoses and CNS-active drug use were common in our study. Lower rates of BPSD diagnoses in non-white compared to white populations may indicate underdiagnosis in clinical settings of treatable conditions. Clinicians' review of prescriptions in this population to reduce poor outcomes is important as is informing care partners on the risks/benefits of using CNS-active drugs.},
}

@article {pmid38668648,
year = {2024},
author = {O'Connor, MK and Aguilar, BJ and Nguyen, A and Berlowitz, D and Zhang, R and Tahami Monfared, AA and Zhang, Q and Xia, W},
title = {The Role of Mental Health Conditions in Early Detection and Treatment of Veterans With Alzheimer's Dementia.},
journal = {Military medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/milmed/usae161},
pmid = {38668648},
issn = {1930-613X},
support = {RF1AG063913/GF/NIH HHS/United States ; RF1AG063913/GF/NIH HHS/United States ; },
abstract = {INTRODUCTION: The benefits of early detection of Alzheimer's disease (AD) have become increasingly recognized. Veterans with mental health conditions (MHCs) may be less likely to receive a specific AD diagnosis compared to veterans without MHCs. We investigated whether rates of MHCs differed between veterans diagnosed with unspecified dementia (UD) vs. AD to better understand the role MHCs might play in establishing a diagnosis of AD.

MATERIALS AND METHODS: This retrospective analysis (2015-2022) identified UD and AD with diagnostic code-based criteria. We determined the proportion of veterans with MHCs in UD vs. AD cohorts. Secondarily, we assessed the distribution of UD/AD diagnoses in veterans with and without MHCs.

RESULTS: We identified 145,309 veterans with UD and 33,996 with AD. The proportion of each MHC was consistently higher in UD vs. AD cohorts: 41.4% vs. 33.2% (depression), 26.9% vs. 20.3% (post-traumatic stress disorder), 23.4% vs. 18.2% (anxiety), 4.3% vs. 2.1% (bipolar disorder), and 3.9% vs. 1.5% (schizophrenia). The UD diagnostic code was used in 84% of veterans with MHCs vs. 78% without MHCs (P < .001).

CONCLUSIONS: Mental health conditions were more likely in veterans with UD vs. AD diagnoses; comorbid MHC may contribute to delayed AD diagnosis.},
}

@article {pmid38668128,
year = {2024},
author = {Liang, C and Paclibar, CG and Gonzaga, NL and Sison, SA and Bath, HS and Biju, AP and Mukherjee, J},
title = {[[125]I]IPC-Lecanemab: Synthesis and Evaluation of Aβ-Plaque-Binding Antibody and Comparison with Small-Molecule [[18]F]Flotaza and [[125]I]IBETA in Postmortem Human Alzheimer's Disease.},
journal = {Neurology international},
volume = {16},
number = {2},
pages = {419-431},
pmid = {38668128},
issn = {2035-8385},
support = {AG079189/NH/NIH HHS/United States ; },
abstract = {Therapeutic antibodies for reducing Aβ plaque load in Alzheimer's disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging a therapeutic antibody, Lecanemab, in a postmortem AD brain anterior cingulate. [[125]I]5-iodo-3-pyridinecarboxamido-Lecanemab ([[125]I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([[125]I]iodo)-3-pyridinecarboxylate with Lecanemab in modest yields. The distinct binding of [[125]I]IPC-Lecanemab to Aβ-rich regions in postmortem human AD brains was higher in grey matter (GM) containing Aβ plaques compared to white matter (WM) (GM/WM was 1.6). Anti-Aβ immunostaining was correlated with [[125]I]IPC-Lecanemab regional binding in the postmortem AD human brains. [[125]I]IPC-Lecanemab binding was consistent with the binding of Aβ small molecules, [[18]F]flotaza and [[125]I]IBETA, in the same subjects. [[18]F]Flotaza and [[125]I]IBETA, however, exhibited significantly higher GM/WM ratios (>20) compared to [[125]I]IPC-Lecanemab. Our results suggest that radiolabeled [[125]I]IPC-Lecanemab retains the ability to bind to Aβ in human AD and may therefore be useful as a PET imaging radiotracer when labeled as [[124]I]IPC-Lecanemab. The ability to directly visualize in vivo a promising therapeutic antibody for AD may be useful in treatment planning and dosing and could be complimentary to small-molecule diagnostic imaging to assess outcomes of therapeutic interventions.},
}

@article {pmid38667783,
year = {2024},
author = {Pires, C and Sapatinha, M and Mendes, R and Bandarra, NM and Gonçalves, A},
title = {Dehydration, Rehydration and Thermal Treatment: Effect on Bioactive Compounds of Red Seaweeds Porphyra umbilicalis and Porphyra linearis.},
journal = {Marine drugs},
volume = {22},
number = {4},
pages = {},
pmid = {38667783},
issn = {1660-3397},
support = {National project I9+ PROALGA : 16-01-03-FMP- 621 0011//MAR2020/ ; },
mesh = {*Porphyra/chemistry ; *Antioxidants/pharmacology/chemistry/isolation & purification ; *Seaweed/chemistry ; *Cholinesterase Inhibitors/pharmacology/isolation & purification ; *Phenols/pharmacology/isolation & purification/analysis ; Flavonoids/pharmacology ; Carotenoids/pharmacology ; Desiccation ; Hot Temperature ; Phycobiliproteins/pharmacology ; Acetylcholinesterase/metabolism ; *Edible Seaweeds ; },
abstract = {The nutritional and bioactive value of seaweeds is widely recognized, making them a valuable food source. To use seaweeds as food, drying and thermal treatments are required, but these treatments may have a negative impact on valuable bioactive compounds. In this study, the effects of dehydration, rehydration, and thermal treatment on the bioactive compounds (carotenoids, phycobiliproteins, total phenolic content (TPC), total flavonoids content (TFC)), antioxidant (ABTS and DPPH radical scavenging activities) and anti-Alzheimer's (Acetylcholinesterase (AchE) inhibitory activities, and color properties of Porphyra umbilicalis and Porphyra linearis seaweeds were evaluated. The results revealed significant reductions in carotenoids, TPC, TFC, and antioxidant activities after the seaweeds' processing, with differences observed between species. Thermal treatment led to the most pronounced reductions in bioactive compound contents and antioxidant activity. AchE inhibitory activity remained relatively high in all samples, with P. umbilicalis showing higher activity than P. linearis. Changes in color (ΔE) were significant after seaweeds' dehydration, rehydration and thermal treatment, especially in P. umbilicalis. Overall, optimizing processing methods is crucial for preserving the bioactive compounds and biological activities of seaweeds, thus maximizing their potential as sustainable and nutritious food sources or as nutraceutical ingredients.},
}

*Porphyra/chemistry
*Antioxidants/pharmacology/chemistry/isolation & purification
*Seaweed/chemistry
*Cholinesterase Inhibitors/pharmacology/isolation & purification
*Phenols/pharmacology/isolation & purification/analysis
Flavonoids/pharmacology
Carotenoids/pharmacology
Desiccation
Hot Temperature
Phycobiliproteins/pharmacology
Acetylcholinesterase/metabolism
*Edible Seaweeds

@article {pmid38666112,
year = {2023},
author = {Dang, C and Wang, Y and Li, Q and Lu, Y},
title = {Neuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers.},
journal = {Psychoradiology},
volume = {3},
number = {},
pages = {kkad009},
pmid = {38666112},
issn = {2634-4416},
abstract = {Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological changes in AD patients occur up to 10-20 years before the emergence of clinical symptoms. Specific diagnosis and appropriate intervention strategies are crucial during the phase of mild cognitive impairment (MCI) and AD. The detection of biomarkers has emerged as a promising tool for tracking the efficacy of potential therapies, making an early disease diagnosis, and prejudging treatment prognosis. Specifically, multiple neuroimaging modalities, including magnetic resonance imaging (MRI), positron emission tomography, optical imaging, and single photon emission-computed tomography, have provided a few potential biomarkers for clinical application. The MRI modalities described in this review include structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy, and arterial spin labelling. These techniques allow the detection of presymptomatic diagnostic biomarkers in the brains of cognitively normal elderly people and might also be used to monitor AD disease progression after the onset of clinical symptoms. This review highlights potential biomarkers, merits, and demerits of different neuroimaging modalities and their clinical value in MCI and AD patients. Further studies are necessary to explore more biomarkers and overcome the limitations of multiple neuroimaging modalities for inclusion in diagnostic criteria for AD.},
}

@article {pmid38663363,
year = {2024},
author = {Yuan, Y and Chang, J and Sun, Q},
title = {Research progress on cognitive frailty in Older Adults with chronic kidney disease.},
journal = {Kidney & blood pressure research},
volume = {},
number = {},
pages = {},
doi = {10.1159/000538689},
pmid = {38663363},
issn = {1423-0143},
abstract = {BACKGROUND: As the medical challenges posed by the ageing population become increasingly severe, the proportion of older people among patients with chronic kidney disease (CKD) is increasing every year. The prevalence of frailty in patients with CKD is significantly higher than that in the general population, and older patients are also a high-risk group for frailty and cognitive impairment. Cognitive frailty, as an important subtype of frailty, is a syndrome characterised by cognitive dysfunction caused by physiological factors, excluding Alzheimer's disease and other types of dementia. It is characterised by the coexistence of physical frailty and cognitive impairment. Previous studies have mainly focused on cognitive impairment, and there is limited research on cognitive frailty, particularly in older patients with CKD.

SUMMARY: This article provides a comprehensive review of the concept, epidemiology, screening methods, prevention and treatment measures and possible pathogenesis of cognitive frailty in patients with CKD.},
}

@article {pmid38663285,
year = {2024},
author = {Waiker, DK and Verma, A and Gajendra, TA and Namrata, and Roy, A and Kumar, P and Trigun, SK and Srikrishna, S and Krishnamurthy, S and Davisson, VJ and Shrivastava, SK},
title = {Design, synthesis, and biological evaluation of some 2-(3-oxo-5,6-diphenyl-1,2,4-triazin-2(3H)-yl)-N-phenylacetamide hybrids as MTDLs for Alzheimer's disease therapy.},
journal = {European journal of medicinal chemistry},
volume = {271},
number = {},
pages = {116409},
doi = {10.1016/j.ejmech.2024.116409},
pmid = {38663285},
issn = {1768-3254},
abstract = {Inspite of established symptomatic relief drug targets, a multi targeting approach is highly in demand to cure Alzheimer's disease (AD). Simultaneous inhibition of cholinesterase (ChE), β secretase-1 (BACE-1) and Dyrk1A could be promising in complete cure of AD. A series of 18 diaryl triazine based molecular hybrids were successfully designed, synthesized, and tested for their hChE, hBACE-1, Dyrk1A and Aβ aggregation inhibitory potentials. Compounds S-11 and S-12 were the representative molecules amongst the series with multi-targeted inhibitory effects. Compound S-12 showed hAChE inhibition (IC50 value = 0.486 ± 0.047 μM), BACE-1 inhibition (IC50 value = 0.542 ± 0.099 μM) along with good anti-Aβ aggregation effects in thioflavin-T assay. Only compound S-02 of the series has shown Dyrk1A inhibition (IC50 value = 2.000 ± 0.360 μM). Compound S-12 has also demonstrated no neurotoxic liabilities against SH-SY5Y as compared to donepezil. The in vivo behavioral studies of the compound S-12 in the scopolamine- and Aβ-induced animal models also demonstrated attanuation of learning and memory functions in rats models having AD-like characteristics. The ex vivo studies, on the rat hippocampal brain demonstrated reduction in certain biochemical markers of the AD brain with a significant increase in ACh level. The Western blot and Immunohistochemistry further revealed lower tau, APP and BACE-1 molecular levels. The drosophilla AD model also revealed improved eyephenotype after treatment with compound S-12. The molecular docking studies of the compounds suggested that compound S-12 was interacting with the ChE-PAS & CAS residues and catalytic dyad residues of the BACE-1 enzymes. The 100 ns molecular dynamics simulation studies of the ligand-protein complexed with hAChE and hBACE-1 also suggested stable ligand-protein confirmation throughout the simulation run.},
}

@article {pmid38663103,
year = {2024},
author = {Nozal, V and Fernández-Gómez, P and García-Rubia, A and Martínez-González, L and Cuevas, EP and Carro, E and Palomo, V and Martínez, A},
title = {Designing multitarget ligands for neurodegenerative diseases with improved permeability trough PLGA nanoencapsulation.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {175},
number = {},
pages = {116626},
doi = {10.1016/j.biopha.2024.116626},
pmid = {38663103},
issn = {1950-6007},
abstract = {Multitarget ligands (MTLs) have emerged as an interesting alternative for addressing complex multifactorial pathologies such as neurodegenerative diseases. However, a common challenge associated with these compounds is often their high molecular weight and low solubility, which becomes a hurdle when trying to permeate over the blood-brain barrier (BBB). In this study, we have designed two new MTLs that modulate three pharmacological targets simultaneously (tau, beta-amyloid and TAR DNA-binding protein 43). To enhance their brain penetration, we have formulated organic polymeric nanoparticles using poly(lactic-co-glycolic acid). The characterization of the formulations, evaluation of their permeability through an in vitro BBB model, and assessment of their activity on disease-representative cellular models, such as Alzheimer's disease and amyotrophic lateral sclerosis, have been conducted. The results demonstrate the potential of the new MTLs and their nanoparticle encapsulation for the treatment of neurodegenerative diseases.},
}

@article {pmid38662500,
year = {2024},
author = {Barbour, AJ and Gourmaud, S and Lancaster, E and Li, X and Stewart, DA and Hoag, KF and Irwin, DJ and Talos, DM and Jensen, FE},
title = {Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awae126},
pmid = {38662500},
issn = {1460-2156},
abstract = {Approximately 22% of Alzheimer's disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition relative to those of excitation would be present in AD patients. We similarly hypothesized that in five times familial AD (5XFAD) mice, the E:I imbalance would progress from an early stage (prodromal) to later symptomatic stages, and be further exacerbated by pentylenetetrazol (PTZ) kindling. Post-mortem AD temporal cortical tissue from patients with or without seizure history were examined for changes in several markers of E:I balance, including levels of the inhibitory GABAA receptor, the sodium potassium chloride cotransporter 1 (NKCC1) and potassium chloride cotransporter 2 (KCC2), and the excitatory NMDA and AMPA type glutamate receptors. We performed patch clamp electrophysiological recordings from CA1 neurons in hippocampal slices and examined the same markers of E:I balance in prodromal 5XFAD mice. We next examined 5XFAD mice at chronic stages, after PTZ or control protocols, and in response to chronic mTORC1 inhibitor rapamycin, administered following kindled seizures, for markers of E:I balance. We found that AD patients with comorbid seizures had worsened cognitive and functional scores and had decreased GABAA receptor subunit expression, and increased NKCC1/KCC2 ratios, indicative of depolarizing GABA responses. Patch clamp recordings of prodromal 5XFAD CA1 neurons showed increased intrinsic excitability, along with decreased GABAergic inhibitory transmission and altered glutamatergic neurotransmission, indicating that E:I imbalance may occur in early disease stages. Furthermore, seizure induction in prodromal 5XFAD mice led to later dysregulation of NKCC1/KCC2 and a reduction in GluA2 AMPA glutamate receptor subunit expression, indicative of depolarizing GABA receptors and calcium permeable AMPA receptors. Finally, we found that chronic treatment with the mTORC1 inhibitor, rapamycin, at doses we have previously shown to attenuate seizure-induced β-amyloid pathology and cognitive deficits, could also reverse elevations to NKCC1/KCC2 ratio in these mice. Our data demonstrate novel mechanisms of interaction between AD and epilepsy and indicate that targeting E:I balance, potentially with FDA-approved mTOR inhibitors, hold therapeutic promise for AD patients with a seizure history.},
}

@article {pmid38661033,
year = {2024},
author = {He, X and Selesnick, I and Zhu, M},
title = {Research Progress of Eye Movement Analyses and its Detection Algorithms in Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050300564240416074025},
pmid = {38661033},
issn = {1875-5828},
abstract = {Alzheimer's disease (AD) has been considered one of the most challenging forms of dementia. The earlier the people are diagnosed with AD, the easier it is for doctors to find a treatment. Based on the previous literature summarizing the research results on the relationship between eye movement and AD before 2013, this paper reviewed 34 original eye movements research papers only closely related to AD published in the past ten years and pointed out that the prosaccade (4 papers) and antisaccade (5 papers) tasks, reading tasks (3 papers), visual search tasks (3 papers) are still the research objects of many researchers, Some researchers have looked at King-Devick tasks (2 papers), reading tasks (3 papers) and special tasks (8 papers), and began to use combinations of different saccade tasks to detect the relationship between eye movement and AD, which had not been done before. These reflect the diversity of eye movement tasks and the complexity and difficulty of the relationship between eye movement and AD. On this basis, the current processing and analysis methods of eye movement datasets are analyzed and discussed in detail, and we note that certain key data that may be especially important for the early diagnosis of AD by using eye movement studies cannot be miss-classified as noise and removed. Finally, we note that the development of methods that can accurately denoise and classify and quickly process massive eye movement data is quite significant for detecting eye movements in early diagnosis of AD.},
}

@article {pmid38660096,
year = {2024},
author = {Kim, T and Kang, DW and Salazar Fajardo, JC and Jang, H and Um, YH and Kim, S and Wang, SM and Kim, D and Lim, HK},
title = {Safety and feasibility of optimized transcranial direct current stimulation in patients with mild cognitive impairment due to Alzheimer's disease: a multicenter study protocol for a randomized controlled trial.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1356073},
pmid = {38660096},
issn = {1664-2295},
abstract = {INTRODUCTION: Transcranial direct current stimulation (tDCS) may effectively preserve and improve cognitive function in patients with mild cognitive impairment (MCI). Research has shown that Individual brain characteristics can influence the effects of tDCS. Computer three-dimensional brain modeling based on magnetic resonance imaging (MRI) has been suggested as an alternative for determining the most accurate tDCS electrode position based on the patients' individual brain characteristics to enhance tDCS effects. Therefore, this study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with Alzheimer's disease (AD)-induced MCI using computer modeling and compare the results with those of a sham group to improve cognitive function.

METHOD: A prospective active-sham group feasibility study was set to recruit 40 participants, who will be randomized into Optimized-tDCS and Sham-tDCS groups. The parameters for tDCS will be 2 mA (disk electrodes R = 1.5 cm) for 30 min during two sets of 15 sessions (2 weeks of resting period in between), using two electrodes in pairs. Using computer modeling, the tDCS electrode positions of each participant will be personalized. Outcome measurements are going to be obtained at three points: baseline, first post-test, and second post-test. The AD assessment scale-cognitive subscale (ADAS-Cog) and the Korean version of Mini-Mental State Examination (K-MMSE), together with other secondary outcomes and safety tests will be used.

DISCUSSION: For the present study, we hypothesize that compared to a sham group, the optimized personalized tDCS application would be effective in improving the cognitive function of patients with AD-induced MCI and the participants would tolerate the tDCS intervention without any significant adverse effects.Clinical trial registration: https://cris.nih.go.kr, identifier [KCT0008918].},
}

@article {pmid38659717,
year = {2024},
author = {Cummings, J and Zhou, Y and Lee, G and Zhong, K and Fonseca, J and Cheng, F},
title = {[Not Available].},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {10},
number = {2},
pages = {e12465},
pmid = {38659717},
issn = {2352-8737},
abstract = {INTRODUCTION: New therapies to prevent or delay the onset of symptoms, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

METHODS: We interrogated clinicaltrials.gov including all clinical trials assessing pharmaceutical therapies for AD active in on January 1, 2024. We used the Common Alzheimer's Disease Research Ontology (CADRO) to classify the targets of therapies in the pipeline.

RESULTS: There are 164 trials assessing 127 drugs across the 2024 AD pipeline. There were 48 trials in Phase 3 testing 32 drugs, 90 trials in Phase 2 assessing 81 drugs, and 26 trials in Phase 1 testing 25 agents. Of the 164 trials, 34% (N = 56) assess disease-modifying biological agents, 41% (N = 68) test disease-modifying small molecule drugs, 10% (N = 17) evaluate cognitive enhancing agents, and 14% (N = 23) test drugs for the treatment of neuropsychiatric symptoms.

DISCUSSION: Compared to the 2023 pipeline, there are fewer trials (164 vs. 187), fewer drugs (127 vs. 141), fewer new chemical entities (88 vs. 101), and a similar number of repurposed agents (39 vs. 40).

HIGHLIGHTS: In the 2024 Alzheimer's disease drug development pipeline, there are 164 clinical trials assessing 127 drugs.The 2024 Alzheimer's disease drug development pipeline has contracted compared to the 2023 Alzheimer pipeline with fewer trials, fewer drugs, and fewer new chemical entities.Drugs in the Alzheimer's disease drug development pipeline target a wide array of targets; the most common processes targeted include neurotransmitter receptors, inflammation, amyloid, and synaptic plasticity.The total development time for a potential Alzheimer's disease therapy to progress from nonclinical studies to FDA review is approximately 13 years.},
}

@article {pmid38659704,
year = {2024},
author = {Wang, S and Xie, S and Zheng, Q and Zhang, Z and Wang, T and Zhang, G},
title = {Biofluid biomarkers for Alzheimer's disease.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1380237},
pmid = {38659704},
issn = {1663-4365},
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.},
}

@article {pmid38659601,
year = {2024},
author = {Yang, LX and Luo, M and Li, SY},
title = {Tanshinone IIA improves Alzheimer's disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis.},
journal = {World journal of psychiatry},
volume = {14},
number = {4},
pages = {563-581},
pmid = {38659601},
issn = {2220-3206},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by oxidative stress and neuroinflammation. Tanshinone IIA (Tan-IIA), a bioactive compound isolated from Salvia miltiorrhiza plants, has shown potential neuroprotective effects; however, the mechanisms underlying such a function remain unclear.

AIM: To investigate potential Tan-IIA neuroprotective effects in AD and to elucidate their underlying mechanisms.

METHODS: Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology. To assess changes in oxidative stress and neuroinflammation, we performed enzyme-linked immunosorbent assay and western blotting. Additionally, the effect of Tan-IIA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Genetic changes related to the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1)/microRNA (miRNA, miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.

RESULTS: In vivo, Tan-IIA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice. In vitro experiments showed that Tan-IIA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability, apoptosis, oxidative stress, and neuroinflammation. In this process, the lncRNA NEAT1 - a potential therapeutic target - is highly expressed in AD mice and downregulated via Tan-IIA treatment. Mechanistically, NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p, which activates nuclear factor kappa-B (NF-κB) signaling, leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein, which exacerbates AD. Tan-IIA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.

CONCLUSION: This study demonstrates that Tan-IIA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway, serving as a foundation for the development of innovative approaches for AD therapy.},
}

@article {pmid38659259,
year = {2024},
author = {Singh, NK and Bhushan, B and Singh, P and Sahu, KK},
title = {Therapeutic Expedition of Luteolin against Brain-related Disorders: An Updated Review.},
journal = {Combinatorial chemistry & high throughput screening},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113862073303342240409060918},
pmid = {38659259},
issn = {1875-5402},
abstract = {Brain-related disorders include neuroinflammation, neurodegenerative disorders, and demyelination, which ultimately affect the quality of life of patients. Currently, brain-related disorders represent the most challenging health problem worldwide due to complex pathogenesis and limited availability of drugs for their management. Further, the available pharmacotherapy accompanies serious side effects, therefore, much attention has been directed toward the development of alternative therapy derived from natural sources to treat such disorders. Recently, flavonoids, natural phytochemicals, have been reported as a treatment option for preventing brain aging and disorders related to this. Among these flavonoids, dietary luteolin, a flavone, is found in many plant products such as broccoli, chamomile tea, and honeysuckle bloom having several pharmacological properties including neuroprotective activities. Therefore, the objective of this paper is to compile the available literature regarding the neuroprotective potential of luteolin and its mechanism of action. Luteolin exerts notable anti-inflammatory, antioxidant, and antiapoptotic activity suggesting its therapeutic efficacy in different neurological disorders. Numerous in-vivo and in-vitro experiments have revealed that luteolin exhibits neuroprotective potential via up-regulating the ER/ERK, PI3AKT, Nrf2 pathways and down-regulating the MAPK/JAK2STAT and NFκB pathways. Taking into account of available facts regarding the neuroprotective efficacy of luteolin, the current study highlights the beneficial effects of luteolin for the prevention, management, and treatment of different neurological disorders. Thus, luteolin can be considered an alternative for the development of new pharmacophores against various brain-related disorders.},
}

@article {pmid38659053,
year = {2024},
author = {Choe, MS and Yeo, HC and Kim, JS and Lee, J and Lee, HJ and Kim, HR and Baek, KM and Jung, NY and Choi, M and Lee, MY},
title = {Simple modeling of familial Alzheimer's disease using human pluripotent stem cell-derived cerebral organoid technology.},
journal = {Stem cell research & therapy},
volume = {15},
number = {1},
pages = {118},
pmid = {38659053},
issn = {1757-6512},
support = {2018R1D1A1A02044017//National Research Fund (KR)/ ; 2020R1A5A2017323//National Research Fund (KR)/ ; 2021R1F1A1047379//National Research Fund (KR)/ ; RS-2023-00223069//National Research Fund (KR)/ ; 2023R1A2C2003446//National Research Fund (KR)/ ; RS-2023-00225239//National Research Fund (KR)/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology/genetics ; *Organoids/metabolism/pathology ; *Pluripotent Stem Cells/metabolism ; *Amyloid beta-Peptides/metabolism/genetics ; Amyloid Precursor Protein Secretases/metabolism/genetics/antagonists & inhibitors ; tau Proteins/metabolism/genetics ; Aspartic Acid Endopeptidases/metabolism/genetics ; Brain/metabolism/pathology ; Models, Biological ; },
abstract = {BACKGROUND: Cerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer's disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening.

METHODS: We established AD hPSC lines from normal hPSCs by introducing genes that harbor familial AD mutations, and the COs were generated using these hPSC lines. The pathological features of AD, including extensive amyloid-β (Aβ) accumulation, tauopathy, and neurodegeneration, were analyzed using enzyme-linked immunosorbent assay, Amylo-Glo staining, thioflavin-S staining, immunohistochemistry, Bielschowsky's staining, and western blot analysis.

RESULTS: The AD COs exhibited extensive Aβ accumulation. The levels of paired helical filament tau and neurofibrillary tangle-like silver deposits were highly increased in the AD COs. The number of cells immunoreactive for cleaved caspase-3 was significantly increased in the AD COs. In addition, treatment of AD COs with BACE1 inhibitor IV, a β-secretase inhibitor, and compound E, a γ-secretase inhibitor, significantly attenuated the AD pathological features.

CONCLUSION: Our model effectively recapitulates AD pathology. Hence, it is a valuable platform for understanding the mechanisms underlying AD pathogenesis and can be used to test the efficacy of anti-AD drugs.},
}

Humans
*Alzheimer Disease/metabolism/pathology/genetics
*Organoids/metabolism/pathology
*Pluripotent Stem Cells/metabolism
*Amyloid beta-Peptides/metabolism/genetics
Amyloid Precursor Protein Secretases/metabolism/genetics/antagonists & inhibitors
tau Proteins/metabolism/genetics
Aspartic Acid Endopeptidases/metabolism/genetics
Brain/metabolism/pathology
Models, Biological

@article {pmid38658547,
year = {2024},
author = {Nicolas, S and Dohm-Hansen, S and Lavelle, A and Bastiaanssen, TFS and English, JA and Cryan, JF and Nolan, YM},
title = {Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats.},
journal = {Translational psychiatry},
volume = {14},
number = {1},
pages = {195},
pmid = {38658547},
issn = {2158-3188},
support = {SFI/FFP/6820//Science Foundation Ireland (SFI)/ ; GOIPD/2018/550//Irish Research Council (An Chomhairle um Thaighde in Éirinn)/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Hippocampus ; *Neurogenesis/physiology ; *Physical Conditioning, Animal/physiology ; Rats ; Male ; *Behavior, Animal/physiology ; Anti-Bacterial Agents/pharmacology ; Rats, Sprague-Dawley ; Sedentary Behavior ; },
abstract = {Lifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer's disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.},
}

Animals
*Gastrointestinal Microbiome/physiology
*Hippocampus
*Neurogenesis/physiology
*Physical Conditioning, Animal/physiology
Rats
Male
*Behavior, Animal/physiology
Anti-Bacterial Agents/pharmacology
Rats, Sprague-Dawley
Sedentary Behavior

@article {pmid38657568,
year = {2024},
author = {Lu, Q and Lv, H and Liu, X and Zang, L and Zhang, Y and Meng, Q},
title = {Lithium therapy's potential to lower dementia risk and the prevalence of Alzheimer's disease: a meta-analysis.},
journal = {European neurology},
volume = {},
number = {},
pages = {},
doi = {10.1159/000538846},
pmid = {38657568},
issn = {1421-9913},
abstract = {INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore we conducted a meta-analysis.

METHODS: A systematic literature review was conducted in PubMed, Embase, and Web of Science. Comparison of the effects of lithium on Alzheimer's disease or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or Alzheimer's disease. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random effects model.

RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of Alzheimer's disease (RR 0.59, 95% CI: 0.44-0.78), and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect the dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It's also uncertain how many prescriptions for lithium treatment lower the chance of dementia development.

CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.},
}

@article {pmid38657528,
year = {2024},
author = {Tamaddon-Abibigloo, Y and Dastmalchi, S and Razzaghi-Asl, N and Shahbazi Mojarrad, J},
title = {Design, synthesis, in vitro and in silico evaluations of new isatin-triazine- aniline hybrids as potent anti- Alzheimer multi-target directed lead compounds.},
journal = {Bioorganic chemistry},
volume = {147},
number = {},
pages = {107355},
doi = {10.1016/j.bioorg.2024.107355},
pmid = {38657528},
issn = {1090-2120},
abstract = {Multi target directed ligands (MTDLs) are one of the promising tools for treatment of complex disease like Alzheimer's disease (AD). In this study, using rational design, we synthesized new 15 hybrids of the s-triazine, isatin and aniline derivatives as anti- AD compounds. The design was as way as that new compounds could had anti cholinesterase (ChE), antioxidant and biometal chelation ability. In vitro biological evaluation against ChE enzymes showed that these molecules were excellent inhibitors with IC50 values ranging from 0.2 nM to 734.5 nM for acetylcholinesterase (AChE), and 0.02 μM to 1.92 μM for butyrylcholinesterase (BChE). Among these compounds, 8 l with IC50 AChE = 0.7 nM, IC50 BChE = 0.09 μM and 8n with IC50 AChE = 0.2 nM, IC50 BChE = 0.03 μM were the most potent compounds. In silico studies showed that these molecules had key and effective interactions with the corresponding enzymes residues. The molecules with hydroxyl group on aniline moiety had also good antioxidant activity with EC50 values ranging from 64.2 μM to 103.6 μM. The UV-Vis spectroscopy study revealed that molecule 8n was also able to chelate biometals such as Zn[2+], Cu[2+]and Fe[2+] properly. It was concluded that these molecules could be excellent lead compounds for future studies.},
}

@article {pmid38657203,
year = {2024},
author = {Evren, AE and Nuha, D and Özkan, BNS and Kahraman, Ç and Gönülalan, EM and Yurttaş, L},
title = {Design and synthesis of phenoxy methyl-oxadiazole compounds against Alzheimer's disease.},
journal = {Archiv der Pharmazie},
volume = {},
number = {},
pages = {e2400115},
doi = {10.1002/ardp.202400115},
pmid = {38657203},
issn = {1521-4184},
support = {//None/ ; },
abstract = {This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti-Alzheimer's agents that occur via cholinesterase and β-secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC50 values of 0.120, 0.039, and 0.063 µM, respectively. However, the compounds showed limited effectiveness against BChE, with only a few compounds exhibiting moderate inhibition. Compound 7e showed an inhibitory effect against BACE-1 close to that of the standard drug. Structural analysis revealed that the compounds with substituted benzothiazole and thiazole moieties exhibited the most promising inhibitory activity. This study provides valuable insights into the potential of these synthesized derivatives as a treatment against Alzheimer's disease. Moreover, the structure, stability, and properties of the active compounds were further investigated using density functional theory calculations. As a final note, the utilization of molecular docking and molecular dynamics simulation studies allowed us to elucidate the action mechanism of the active compounds and gain insights into the structure-activity relationship against AChE and β-secretase proteins. These computational techniques provide valuable information on the binding modes, interactions with target enzymes, dynamic behavior, and conformational changes of the compounds, enabling a comprehensive understanding of their biological activity.},
}

@article {pmid38655427,
year = {2024},
author = {Yazdanpanah, F and Jackson, AC and Sanaie, N and Sharifi, F and Shamshirgaran, SM and Bahramnezhad, F},
title = {The epidemiology and treatment outcomes of COVID-19 patients admitted to an intensive care unit in an Iranian hospital in Neyshabur city.},
journal = {Health science reports},
volume = {7},
number = {4},
pages = {e2049},
pmid = {38655427},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: The COVID-19 pandemic and the infection of numerous individuals from diverse societies have emerged as major global challenges. Given the limited resources in intensive care units, effective bed management and resource allocation require a deep understanding of the disease. This study aimed to assess the epidemiology and treatment outcomes of COVID-19 patients admitted to an intensive care unit in an Iranian hospital in Neyshabur city.

METHODS: This cross-sectional study was conducted on COVID-19 patients hospitalized in intensive care units in Razavi Khorasan, Iran in 2021. Census sampling was used to include all intensive care units. Of the initial 480 cases, 54 cases were excluded based on the exclusion criteria, leaving 426 cases for the study. Data were collected with the help of a data collection form that was designed by the researcher and its content validity and reliability were measured with Cronbach's alpha coefficient (α = 89%.). Data were analyzed with SPSS version 20 software. Descriptive and inferential statistics were used to analyze the data. Mean, standard deviation, and interquartile range indicators were used for descriptive statistics, and absolute frequency and relative frequency (percentage) were used to show numbers and ratios.

RESULTS: The mean (SD) age of the patients was 66.33 (15.05) years, and 49.3% were female. The results showed that arterial blood oxygen saturation, respiratory rate, and Alzheimer's disease were significant variables for predicting mortality. Furthermore, arterial blood oxygen saturation, respiratory rate, and the need for transfusion of blood products were significant variables in predicting hospitalization and the risk of acute respiratory distress syndrome (ARDS).

CONCLUSION: This study demonstrated that arterial blood oxygen saturation, respiratory rate, and Alzheimer's disease are crucial variables for predicting death. Furthermore, arterial blood oxygen saturation and respiratory rate are significant factors in predicting the risk of ARDS.},
}

@article {pmid38654507,
year = {2024},
author = {Peng, Y and Chen, Q and Xue, YH and Jin, H and Liu, S and Du, MQ and Yao, SY},
title = {Ginkgo biloba and Its Chemical Components in the Management of Alzheimer's Disease.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-42},
doi = {10.1142/S0192415X24500277},
pmid = {38654507},
issn = {1793-6853},
abstract = {The pathogenesis of Alzheimer's disease (AD), a degenerative disease of the central nervous system, remains unclear. The main manifestations of AD include cognitive and behavioral disorders, neuropsychiatric symptoms, neuroinflammation, amyloid plaques, and neurofibrillary tangles. However, current drugs for AD once the dementia stage has been reached only treat symptoms and do not delay progression, and the research and development of targeted drugs for AD have reached a bottleneck. Thus, other treatment options are needed. Bioactive ingredients derived from plants are promising therapeutic agents. Specifically, Ginkgo biloba (Gb) extracts exert anti-oxidant, anticancer, neuroplastic, neurotransmitter-modulating, blood fluidity, and anti-inflammatory effects, offering alternative options in the treatment of cardiovascular, metabolic, and neurodegenerative diseases. The main chemical components of Gb include flavonoids, terpene lactones, proanthocyanidins, organic acids, polysaccharides, and amino acids. Gb and its extracts have shown remarkable therapeutic effects on various neurodegenerative diseases, including AD, with few adverse reactions. Thus, high-quality Gb extracts are a well-established treatment option for AD. In this review, we summarize the insights derived from traditional Chinese medicine, experimental models, and emerging clinical trials on the role of Gb and its chemical components in the treatment of the main clinical manifestations of AD.},
}

@article {pmid38653878,
year = {2024},
author = {He, Y and Wang, Y and Li, X and Qi, Y and Qu, Z and Hu, Y},
title = {Lycium Barbarum Polysaccharides Improves Cognitive Functions in ICV-STZ-Induced Alzheimer's Disease Mice Model by Improving the Synaptic Structural Plasticity and Regulating IRS1/PI3K/AKT Signaling Pathway.},
journal = {Neuromolecular medicine},
volume = {26},
number = {1},
pages = {15},
pmid = {38653878},
issn = {1559-1174},
support = {No. 82260712//the National Natural Science Foundation of China/ ; No. 82260712//the National Natural Science Foundation of China/ ; No. 82260712//the National Natural Science Foundation of China/ ; No. 82260712//the National Natural Science Foundation of China/ ; No. 82260712//the National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Insulin Receptor Substrate Proteins/metabolism ; Male ; *Alzheimer Disease/chemically induced/drug therapy ; Mice ; *Signal Transduction/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Mice, Inbred C57BL ; *Phosphatidylinositol 3-Kinases/metabolism ; *Disease Models, Animal ; *Neuronal Plasticity/drug effects ; *tau Proteins/metabolism ; Streptozocin ; Neuroprotective Agents/therapeutic use/pharmacology ; Cognition/drug effects ; Amyloid beta-Peptides/metabolism ; Phosphorylation/drug effects ; Synapses/drug effects ; Insulin Resistance ; Brain/drug effects/metabolism/pathology ; },
abstract = {Lycium barbarum polysaccharide (LBP) have a certain curative effect on hypoglycemic and neuroprotective effects, but the specific mechanism is unclear and needs to be further explored. This study aimed to clarify the mechanisms of LBP in the treatment of ICV-STZ mice model of AD from the perspectives of insulin resistance, IRS1/PI3K/AKT signaling pathway, and synaptic protein expression. We used male C57BL/6J mice injected with STZ (3 mg/kg) in the lateral ventricle as an AD model. After treatment with LBP, the learning and memory abilities of ICV-STZ mice were enhanced, and the pathological changes in brain tissue were alleviated. LBP can regulate the expression of proteins related to the IRS1/PI3K/AKT signaling pathway and thereby reducing Aβ deposition and tau protein phosphorylation in the brain of ICV-STZ mice. In addition, LBP also can up-regulate the expression of synaptic proteins. The results indicated that LBP played a neuroprotective role by regulating the IRS1/PI3K/AKT pathway, inhibiting tau protein hyperphosphorylation and improving the expression levels of synapse-related proteins.},
}

Animals
*Insulin Receptor Substrate Proteins/metabolism
Male
*Alzheimer Disease/chemically induced/drug therapy
Mice
*Signal Transduction/drug effects
*Proto-Oncogene Proteins c-akt/metabolism
*Drugs, Chinese Herbal/therapeutic use/pharmacology
*Mice, Inbred C57BL
*Phosphatidylinositol 3-Kinases/metabolism
*Disease Models, Animal
*Neuronal Plasticity/drug effects
*tau Proteins/metabolism
Streptozocin
Neuroprotective Agents/therapeutic use/pharmacology
Cognition/drug effects
Amyloid beta-Peptides/metabolism
Phosphorylation/drug effects
Synapses/drug effects
Insulin Resistance
Brain/drug effects/metabolism/pathology

@article {pmid38653355,
year = {2024},
author = {Mey, M and Bhatta, S and Suresh, S and Labrador, LM and Piontkivska, H and Casadesus, G},
title = {Therapeutic benefits of central LH receptor agonism in the APP/PS1 AD model involve trophic and immune regulation and reproductive status dependent.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {167165},
doi = {10.1016/j.bbadis.2024.167165},
pmid = {38653355},
issn = {1879-260X},
abstract = {The mechanisms that underly reproductive hormone effects on cognition, neuronal plasticity, and AD risk, particularly in relation to gonadotropin LH receptor (LHCGR) signaling, remain poorly understood. To address this knowledge gap and clarify the impact of circulating steroid hormones the therapeutic effects of CNS LHCGR activation, we delivered the LHCGR agonist human chorionic gonadotropin (hCG) intracerebroventricularly (ICV) and evaluated functional, structural, plasticity-related signaling cascades, Aβ pathology, and transcriptome differences in reproductively intact and ovariectomized (OVX) APP/PS1 AD female mice. Here we demonstrate that CNS hCG delivery restored function to wild-type levels only in OVX APP/PS1 mice. Spine density was increases in all hCG treated groups independently of reproductive status. Notably, increases in BDNF signaling, like cognition, were selectively upregulated only in the OVX hCG-treated group. RNA sequencing analyses identified a significant increase in peripheral myeloid and pro-inflammatory genes within the hippocampi of the OVX group that were completely reversed by hCG, identifying a potential mechanism underlying the selective therapeutic effect of LHCGR activation. Interestingly, in intact mice, hCG administration mimicked the effects of gonadectomy. Together, our findings indicate that CNS LHCGR agonism in the post-menopausal context is beneficial through trophic and immune mechanisms. Our findings also underscore the presence of a steroid-LHCGR mechanistic interaction that is unexplored yet potentially meaningful to fully understand "post-menopausal" brain function and CNS hormone treatment response.},
}

@article {pmid38652180,
year = {2024},
author = {Ansari, S and Etekochay, MO and Atanasov, AG and Prasad, VP and Kandimalla, R and Mofatteh, M and V, P and Emran, TB},
title = {Human olfactory neurosphere-derived cells: A unified tool for neurological disease modelling and neurotherapeutic applications.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000001460},
pmid = {38652180},
issn = {1743-9159},
abstract = {As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened.},
}

@article {pmid38652179,
year = {2024},
author = {Yamada, K and Iwatsubo, T},
title = {Involvement of the glymphatic/meningeal lymphatic system in Alzheimer's disease: insights into proteostasis and future directions.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {81},
number = {1},
pages = {192},
pmid = {38652179},
issn = {1420-9071},
mesh = {*Alzheimer Disease/metabolism/pathology ; Humans ; *Glymphatic System/metabolism/pathology ; *Meninges/metabolism/pathology ; *Proteostasis ; *Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; Animals ; Lymphatic System/metabolism/pathology ; Brain/metabolism/pathology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is pathologically characterized by the abnormal accumulation of Aβ and tau proteins. There has long been a keen interest among researchers in understanding how Aβ and tau are ultimately cleared in the brain. The discovery of this glymphatic system introduced a novel perspective on protein clearance and it gained recognition as one of the major brain clearance pathways for clearing these pathogenic proteins in AD. This finding has sparked interest in exploring the potential contribution of the glymphatic/meningeal lymphatic system in AD. Furthermore, there is a growing emphasis and discussion regarding the possibility that activating the glymphatic/meningeal lymphatic system could serve as a novel therapeutic strategy against AD.

OBJECTIVES:  Given this current research trend, the primary focus of this comprehensive review is to highlight the role of the glymphatic/meningeal lymphatic system in the pathogenesis of AD. The discussion will encompass future research directions and prospects for treatment in relation to the glymphatic/meningeal lymphatic system.},
}

*Alzheimer Disease/metabolism/pathology
Humans
*Glymphatic System/metabolism/pathology
*Meninges/metabolism/pathology
*Proteostasis
*Amyloid beta-Peptides/metabolism
tau Proteins/metabolism
Animals
Lymphatic System/metabolism/pathology
Brain/metabolism/pathology

@article {pmid38652148,
year = {2024},
author = {Liyanage, NS and Awwad, F and Gonçalves Dos Santos, KC and Jayawardena, TU and Mérindol, N and Desgagné-Penix, I},
title = {Navigating Amaryllidaceae Alkaloids: Bridging Gaps and Charting Biosynthetic Territories - A Comprehensive Review.},
journal = {Journal of experimental botany},
volume = {},
number = {},
pages = {},
doi = {10.1093/jxb/erae187},
pmid = {38652148},
issn = {1460-2431},
abstract = {Amaryllidaceae alkaloid (AAs) biosynthesis has garnered significant attention in recent years, particularly with the commercialisation of galanthamine as a treatment for the symptoms of Alzheimer's disease. A significant amount of research work over the last 8 decades has focused on the understanding of AA biosynthesis, starting from early radiolabelling studies to recent multi-omics analysis with modern biotechnological advancements. Those studies enabled the identification of hundreds of metabolites, the characterisation of biochemical pathway, an understanding of the environmental stimuli, and of the molecular regulation of these pharmaceutically and agriculturally important metabolites. Despite the numerous works there remain significant gaps in understanding their biosynthesis in Amaryllidaceae plants. As such, further research is needed to fully elucidate the metabolic pathway and facilitate their production. This review aims to provide a comprehensive overall summary of the current state of knowledge on AAs biosynthesis, from elicitation of transcription factors expression in the cell nucleus to alkaloid transport in the apoplast, and to highlight the challenges that need to be overcome for further advancement.},
}

@article {pmid38651489,
year = {2024},
author = {Marinova, P and Tamahkyarova, K},
title = {Synthesis and Biological Activities of Some Metal Complexes of Peptides: A Review.},
journal = {Biotech (Basel (Switzerland))},
volume = {13},
number = {2},
pages = {},
pmid = {38651489},
issn = {2673-6284},
support = {project СП 23-ХФ-006//We acknowledge the financial support from the Fund for Scientific Research of the Plovdiv University/ ; },
abstract = {Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versatile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The research of the better part of the cited papers was conducted using various database platforms such as MetalPDB. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for understanding the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer's, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal complexes have potential applications as radiopharmaceuticals. The examination of these complexes was achieved by preforming UV-Vis, IR, EPR, NMR spectroscopy, and X-ray analysis. This summary, although unable to cover all of the studies in the field, offers a review of the ongoing experimentation and is a basis for new ideas, as well as strategies to explore and gain knowledge from the extensive realm of peptide-chelated metals and biotechnologies.},
}

@article {pmid38651179,
year = {2024},
author = {Li, J and Wu, Z and Wu, Y and Hu, XY and Yang, J and Zhu, D and Wu, M and Li, X and Bentum-Ennin, L and Hu, W},
title = {IL-22, a vital cytokine in autoimmune diseases.},
journal = {Clinical and experimental immunology},
volume = {},
number = {},
pages = {},
doi = {10.1093/cei/uxae035},
pmid = {38651179},
issn = {1365-2249},
abstract = {Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.},
}

@article {pmid38649866,
year = {2024},
author = {Jiang, S and Cai, G and Yang, Z and Shi, H and Zeng, H and Ye, Q and Hu, Z and Wang, Z},
title = {Biomimetic Nanovesicles as a Dual Gene Delivery System for the Synergistic Gene Therapy of Alzheimer's Disease.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.3c13150},
pmid = {38649866},
issn = {1936-086X},
abstract = {The association between dysfunctional microglia and amyloid-β (Aβ) is a fundamental pathological event and increases the speed of Alzheimer's disease (AD). Additionally, the pathogenesis of AD is intricate and a single drug may not be enough to achieve a satisfactory therapeutic outcome. Herein, we reported a facile and effective gene therapy strategy for the modulation of microglia function and intervention of Aβ anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). The biomimetic nanovesicles codelivery β-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) and TREM2 plasmid (pTREM2) gene drug efficiently penetrate the blood-brain barrier and enhance the drug accumulation at AD lesions with the help of exosomes homing ability and angiopep-2 peptides. Specifically, an upregulation of TREM2 expression can reprogram microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype while also restoring its capacity to phagocytose Aβ and its nerve repair function. In addition, siRNA reduces the production of Aβ plaques at the source by knocking out the BACE1 gene, which is expected to further enhance the therapeutic effect of AD. The in vivo study suggests that TSEL through the synergistic effect of two gene drugs can ameliorate APP/PS1 mice cognitive impairment by regulating the activated microglial phenotype, reducing the accumulation of Aβ, and preventing the retriggering of neuroinflammation. This strategy employs biomimetic nanovesicles for the delivery of dual nucleic acids, achieving synergistic gene therapy for AD, thus offering more options for the treatment of AD.},
}

@article {pmid38649307,
year = {2024},
author = {Pang, C and Wang, R and Liu, K and Yuan, X and Ni, J and Cao, Q and Chen, Y and Dong, PL and Han, H},
title = {Serum and urine metabolomics based on UPLC-QTOF/MS reveal the effect and potential mechanism of "schisandra-evodia" herb pair in the treatment of Alzheimer's disease.},
journal = {Biomedical chromatography : BMC},
volume = {},
number = {},
pages = {e5882},
doi = {10.1002/bmc.5882},
pmid = {38649307},
issn = {1099-0801},
support = {LH2019H053//Natural Science Foundation of Heilongjiang Province/ ; 2017XY01//Heilongjiang University of Traditional Chinese Medicine Scientific Research Fund Project/ ; },
abstract = {The "schisandra-evodia" herb pair (S-E) is a herbal preparation to treat Alzheimer's disease (AD). This study aims to investigate the therapeutic efficacy and potential mechanism of S-E in AD rats, utilizing pharmacodynamic assessments and serum- and urine-based metabolomic analyses. Pharmacodynamic assessments included Morris water maze test, hematoxylin-eosin staining and immunohistochemistry experiments. The results of the study showed that the AD model was successful; the S-E significantly enhanced long-term memory and spatial learning in AD rats. Meanwhile, S-E notably ameliorated Aβ25-35-induced cognitive impairment, improved hippocampal neuron morphology, decreased Aβ deposition in the hippocampus and mitigated inflammatory damage. We then analyzed serum and urine samples using UPLC-MS/MS to identify potential biomarkers and metabolic pathways. Metabolomic analysis revealed alterations in 40 serum metabolites and 38 urine metabolites following S-E treatment, predominantly affecting pathways related to taurine and hypotaurine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism and arachidonic acid metabolism. This study elucidates the biochemical mechanism underlying AD and the metabolic pathway influenced by S-E, laying the groundwork for future clinical applications.},
}

@article {pmid38649269,
year = {2024},
author = {Murakami, R and Watanabe, H and Hashimoto, H and Kashiwagi-Hakozaki, M and Hashimoto, T and Karch, CM and , and Iwatsubo, T and Okano, H},
title = {Inhibitory roles of Apolipoprotein E Christchurch astrocytes in curbing tau propagation using human pluripotent stem cell-derived models.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.1709-23.2024},
pmid = {38649269},
issn = {1529-2401},
abstract = {Genetic variants in the apolipoprotein E (APOE) gene affect the onset and progression of Alzheimer's disease (AD). The APOE Christchurch (APOE Ch) variant has been identified as the most prominent candidate for preventing the onset and progression of AD. In this study, we generated isogenic APOE3Ch/3Ch human induced pluripotent stem cells (iPSCs) from APOE3/3 healthy control female iPSCs and induced them into astrocytes. RNA expression analysis revealed the inherent resilience of APOE3Ch/3Ch astrocytes to induce a reactive state in response to inflammatory cytokines. Moreover, cytokine treatment changed astrocytic morphology with more complexity in APOE3/3 astrocytes, but not in APOE3Ch/3Ch astrocytes, indicating resilience of the rare variant to a reactive state. Interestingly, we observed robust morphological alterations containing more intricate processes when cocultured with iPSC-derived cortical neurons, in which APOE3Ch/3Ch astrocytes reduced complexity compared with APOE3/3 astrocytes. To assess the impacts of tau propagation effects, we next developed a sophisticated and sensitive assay utilizing cortical neurons derived from human iPSCs, previously generated from donors of both sexes. We showed that APOE3Ch/3Ch astrocytes effectively mitigated tau propagation within iPSC-derived neurons. This study provides important experimental evidence of the characteristic functions exhibited by APOE3Ch/3Ch astrocytes, thereby offering valuable insights for the advancement of novel clinical interventions in AD research.Significance Statement Alzheimer's disease (AD) is a degenerative disease that causes cognitive decline. Familial AD is a severe form caused by mutations in the PSEN1, PSEN2, or APP genes. One carrier of the PSEN1 mutation did not develop dementia. This carrier also had a rare variant of the APOE gene, the Christchurch variant. The APOE Christchurch variant may protect against familial AD. The mechanism of this protection is not fully understood. In the present study, we have successfully demonstrated that the APOE Christchurch variant suppresses the propagation of tau and exhibits a diminished capacity to convert native astrocytes into reactive astrocytes. These significant findings contribute novel insights to the field of the APOE gene and AD research.},
}

@article {pmid38648920,
year = {2024},
author = {Reid, GA and Darvesh, S},
title = {Interaction of Exogenous Acetylcholinesterase and Butyrylcholinesterase with Amyloid-β Plaques in Human Brain Tissue.},
journal = {Chemico-biological interactions},
volume = {},
number = {},
pages = {111012},
doi = {10.1016/j.cbi.2024.111012},
pmid = {38648920},
issn = {1872-7786},
abstract = {Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are associated with amyloid-β (Aβ) plaques and exhibit altered biochemical properties in human Alzheimer's disease (AD), as well as in the transgenic 5XFAD mouse model of AD amyloidosis. In the brains of the 5XFAD mouse model devoid of BChE enzyme (5XFAD/BChE-KO), incubation of tissue sections with exogenous BChE purified from human plasma (pl-BChE) leads to its association with Aβ plaques and its biochemical properties are comparable to those reported for endogenous BChE associated with plaques in both human AD and in 5XFAD mouse brain tissue. We sought to determine whether these observations in 5XFAD/BChE-KO mice also apply to human brain tissues. To do so, endogenous ChE activity in human AD brain tissue sections was quenched with 50% aqueous acetonitrile (MeCNaq) leaving the tissue intact for further studies. Quenched sections were then incubated with recombinant AChE (r-AChE) or pl-BChE and stained for each enzymes' activity. Exogenous r-AChE or pl-BChE became associated with Aβ plaques, and when bound, had properties that were comparable to the endogenous ChE enzymes associated with plaques in AD brain tissues without acetonitrile treatment. These findings in human AD brain tissue extend previous observations in the 5XFAD/BChE-KO mouse model and demonstrate that exogenously applied r-AChE and pl-BChE have high affinity for Aβ plaques in human brain tissues. This association alters the biochemical properties of these enzymes, most likely due a conformational change. If incorporation of AChE and BChE in Aβ plaques facilitates AD pathogenesis, blocking this association could lead to disease-modifying approaches to AD. This work provides a method to study the mechanism of AChE and BChE interaction with Aβ plaque pathology in post-mortem human brain tissue.},
}

@article {pmid38648267,
year = {2024},
author = {Salvador, AFM and Abduljawad, N and Kipnis, J},
title = {Meningeal Lymphatics in Central Nervous System Diseases.},
journal = {Annual review of neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-neuro-113023-103045},
pmid = {38648267},
issn = {1545-4126},
abstract = {Since its recent discovery, the meningeal lymphatic system has reshaped our understanding of central nervous system (CNS) fluid exchange, waste clearance, immune cell trafficking, and immune privilege. Meningeal lymphatics have also been demonstrated to functionally modify the outcome of neurological disorders and their responses to treatment, including brain tumors, inflammatory diseases such as multiple sclerosis, CNS injuries, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review, we discuss recent evidence of the contribution of meningeal lymphatics to neurological diseases, as well as the available experimental methods for manipulating meningeal lymphatics in these conditions. Finally, we also provide a discussion of the pressing questions and challenges in utilizing meningeal lymphatics as a prime target for CNS therapeutic intervention and possibly drug delivery for brain disorders.},
}

@article {pmid38647433,
year = {2024},
author = {Mousavi, H and Rimaz, M and Zeynizadeh, B},
title = {Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.4c00055},
pmid = {38647433},
issn = {1948-7193},
abstract = {Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH2NH2•H2O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2[(G2019S)], hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC50, EC50, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.},
}

@article {pmid38647399,
year = {2024},
author = {Lin, RR and Jin, LL and Xue, YY and Zhang, ZS and Huang, HF and Chen, DF and Liu, Q and Mao, ZW and Wu, ZY and Tao, QQ},
title = {Hybrid Membrane-Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e2306675},
doi = {10.1002/advs.202306675},
pmid = {38647399},
issn = {2198-3844},
support = {2021ZD0201103//Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Projects/ ; 2021ZD0201803//Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Projects/ ; 2024SSYS0018//Key R&D Program of Zhejiang Province/ ; LBY21H090003//Natural Science Foundation of Zhejiang Province/ ; 2022ZDYF22//Key Science & Technologies R&D Program of Lishui City/ ; },
abstract = {The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.},
}

@article {pmid38646507,
year = {2024},
author = {Zhang, X and Zhu, Z and Huang, Y and Shang, X and O'Brien, TJ and Kwan, P and Ha, J and Wang, W and Liu, S and Zhang, X and Kiburg, K and Bao, Y and Wang, J and Yu, H and He, M and Zhang, L},
title = {Shared genetic aetiology of Alzheimer's disease and age-related macular degeneration by APOC1 and APOE genes.},
journal = {BMJ neurology open},
volume = {6},
number = {1},
pages = {e000570},
pmid = {38646507},
issn = {2632-6140},
abstract = {BACKGROUND: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share similar pathological features, suggesting common genetic aetiologies between the two. Investigating gene associations between AD and AMD may provide useful insights into the underlying pathogenesis and inform integrated prevention and treatment for both diseases.

METHODS: A stratified quantile-quantile (QQ) plot was constructed to detect the pleiotropy among AD and AMD based on genome-wide association studies data from 17 008 patients with AD and 30 178 patients with AMD. A Bayesian conditional false discovery rate-based (cFDR) method was used to identify pleiotropic genes. UK Biobank was used to verify the pleiotropy analysis. Biological network and enrichment analysis were conducted to explain the biological reason for pleiotropy phenomena. A diagnostic test based on gene expression data was used to predict biomarkers for AD and AMD based on pleiotropic genes and their regulators.

RESULTS: Significant pleiotropy was found between AD and AMD (significant leftward shift on QQ plots). APOC1 and APOE were identified as pleiotropic genes for AD-AMD (cFDR <0.01). Network analysis revealed that APOC1 and APOE occupied borderline positions on the gene co-expression networks. Both APOC1 and APOE genes were enriched on the herpes simplex virus 1 infection pathway. Further, machine learning-based diagnostic tests identified that APOC1, APOE (areas under the curve (AUCs) >0.65) and their upstream regulators, especially ZNF131, ADNP2 and HINFP, could be potential biomarkers for both AD and AMD (AUCs >0.8).

CONCLUSION: In this study, we confirmed the genetic pleiotropy between AD and AMD and identified APOC1 and APOE as pleiotropic genes. Further, the integration of multiomics data identified ZNF131, ADNP2 and HINFP as novel diagnostic biomarkers for AD and AMD.},
}

@article {pmid38646460,
year = {2024},
author = {Shaheen, H and Melnik, R and Singh, S and , },
title = {Data-driven Stochastic Model for Quantifying the Interplay Between Amyloid-beta and Calcium Levels in Alzheimer's Disease.},
journal = {Statistical analysis and data mining},
volume = {17},
number = {2},
pages = {},
pmid = {38646460},
issn = {1932-1864},
support = {U01 AG024904/AG/NIA NIH HHS/United States ; },
abstract = {The abnormal aggregation of extracellular amyloid-β(Aβ) in senile plaques resulting in calcium Ca+2 dyshomeostasis is one of the primary symptoms of Alzheimer's disease (AD). Significant research efforts have been devoted in the past to better understand the underlying molecular mechanisms driving Aβ deposition and Ca+2 dysregulation. Importantly, synaptic impairments, neuronal loss, and cognitive failure in AD patients are all related to the buildup of intraneuronal Aβ accumulation. Moreover, increasing evidence show a feed-forward loop between Aβ and Ca+2 levels, i.e. Aβ disrupts neuronal Ca+2 levels, which in turn affects the formation of Aβ. To better understand this interaction, we report a novel stochastic model where we analyze the positive feedback loop between Aβ and Ca+2 using ADNI data. A good therapeutic treatment plan for AD requires precise predictions. Stochastic models offer an appropriate framework for modelling AD since AD studies are observational in nature and involve regular patient visits. The etiology of AD may be described as a multi-state disease process using the approximate Bayesian computation method. So, utilizing ADNI data from 2-year visits for AD patients, we employ this method to investigate the interplay between Aβ and Ca+2 levels at various disease development phases. Incorporating the ADNI data in our physics-based Bayesian model, we discovered that a sufficiently large disruption in either Aβ metabolism or intracellular Ca+2 homeostasis causes the relative growth rate in both Ca+2 and Aβ, which corresponds to the development of AD. The imbalance of Ca+2 ions causes Aβ disorders by directly or indirectly affecting a variety of cellular and subcellular processes, and the altered homeostasis may worsen the abnormalities of Ca+2 ion transportation and deposition. This suggests that altering the Ca+2 balance or the balance between Aβ and Ca+2 by chelating them may be able to reduce disorders associated with AD and open up new research possibilities for AD therapy.},
}

@article {pmid38645989,
year = {2024},
author = {Peng, Y and Zhou, C},
title = {Network Pharmacology and Molecular Docking Identify the Potential Mechanism and Therapeutic Role of Scutellaria baicalensis in Alzheimer's Disease.},
journal = {Drug design, development and therapy},
volume = {18},
number = {},
pages = {1199-1219},
pmid = {38645989},
issn = {1177-8881},
mesh = {*Alzheimer Disease/drug therapy/metabolism ; *Scutellaria baicalensis/chemistry ; Humans ; *Molecular Docking Simulation ; *Network Pharmacology ; Drugs, Chinese Herbal/pharmacology/chemistry ; STAT3 Transcription Factor/metabolism/antagonists & inhibitors ; Plant Extracts/pharmacology/chemistry ; },
abstract = {AIM: Scutellaria baicalensis, a traditional Chinese medicinal herb renowned for its anti-inflammatory, antioxidant, and anti-tumor properties, has shown promise in alleviating cognitive impairment associated with Alzheimer's disease. Nonetheless, the exact neuroprotective mechanism of Scutellaria baicalensis against Alzheimer's disease remains unclear. In this study, network pharmacology was employed to explore the possible mechanisms by which Scutellaria baicalensis protects against Alzheimer's disease.

METHODS: The active compounds of Scutellaria baicalensis were retrieved from the TCMSP database, and their corresponding targets were identified. Alzheimer's disease-related targets were obtained through searches in the GeneCards and OMIM databases. Cytoscape 3.6.0 software was utilized to construct a regulatory network illustrating the "active ingredient-target" relationships. Subsequently, the target genes affected by Scutellaria baicalensis in the context of Alzheimer's disease were input into the String database to establish a PPI network. GO analysis and KEGG analysis were conducted using the DAVID database to predict the potential pathways associated with these key targets. Following this, the capacity of these active ingredients to bind to core targets was confirmed through molecular docking. In vitro experiments were then carried out for further validation.

RESULTS: A total of 36 active ingredients from Scutellaria baicalensis were screened out, which corresponded to 365 targets. Molecular docking results demonstrated the robust binding abilities of Baicalein, Wogonin, and 5,2'-Dihydroxy-6,7,8-trimethoxyflavone to key target proteins (SRC, PIK3R1, and STAT3). In vitro experiments showed that the active components of Scutellaria baicalensis can inhibit STAT3 expression by downregulating the PIK3R1/SRC pathway in Neuro 2A cells.

CONCLUSION: In summary, these findings collectively suggest that Scutellaria baicalensis holds promise as a viable treatment option for Alzheimer's disease.},
}

*Alzheimer Disease/drug therapy/metabolism
*Scutellaria baicalensis/chemistry
Humans
*Molecular Docking Simulation
*Network Pharmacology
Drugs, Chinese Herbal/pharmacology/chemistry
STAT3 Transcription Factor/metabolism/antagonists & inhibitors
Plant Extracts/pharmacology/chemistry

@article {pmid38645748,
year = {2024},
author = {Yap, LE and Hunt, JE and Turner, RS},
title = {Aging as a target for the prevention and treatment of Alzheimer's disease.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1376104},
pmid = {38645748},
issn = {1664-2295},
abstract = {Alzheimer's disease (AD), the most common etiology of dementia in older adults, is projected to double in prevalence over the next few decades. Current treatments for AD manage symptoms or slow progressive decline, but are accompanied by significant inconvenience, risk, and cost. Thus, a better understanding of the risk factors and pathophysiology of AD is needed to develop novel prevention and treatment strategies. Aging is the most important risk factor for AD. Elucidating molecular mechanisms of aging may suggest novel therapeutic targets. While aging is inevitable, it may be accelerated by caloric excess and slowed by caloric restriction (CR) or intermittent fasting. As such, CR may slow aging and reduce the risk of all diseases of aging, including dementia due to AD. The literature on CR, intermittent fasting, and treatment with polyphenols such as resveratrol-a pharmacologic CR-mimetic-supports this hypothesis based on clinical outcomes as well as biomarkers of aging and AD. More studies exploring the role of CR in regulating aging and AD progression in man are needed to fill gaps in our understanding and develop safer and more effective strategies for the prevention and treatment of AD.},
}

@article {pmid38645276,
year = {2024},
author = {Okafor, M and Champomier, O and Raibaut, L and Ozkan, S and El Kholti, N and Ory, S and Chasserot-Golaz, S and Gasman, S and Hureau, C and Faller, P and Vitale, N},
title = {Restoring cellular copper homeostasis in Alzheimer disease: a novel peptide shuttle is internalized by an ATP-dependent endocytosis pathway involving Rab5- and Rab14-endosomes.},
journal = {Frontiers in molecular biosciences},
volume = {11},
number = {},
pages = {1355963},
pmid = {38645276},
issn = {2296-889X},
abstract = {CPPs, or Cell-Penetrating Peptides, offer invaluable utility in disease treatment due to their ability to transport various therapeutic molecules across cellular membranes. Their unique characteristics, such as biocompatibility and low immunogenicity, make them ideal candidates for delivering drugs, genes, or imaging agents directly into cells. This targeted delivery enhances treatment efficacy while minimizing systemic side effects. CPPs exhibit versatility, crossing biological barriers and reaching intracellular targets that conventional drugs struggle to access. This capability holds promise in treating a wide array of diseases, including cancer, neurodegenerative disorders, and infectious diseases, offering a potent avenue for innovative and targeted therapies, yet their precise mechanism of cell entry is far from being fully understood. In order to correct Cu dysregulation found in various pathologies such as Alzheimer disease, we have recently conceived a peptide Cu(II) shuttle, based on the αR5W4 CPP, which, when bound to Cu(II), is able to readily enter a neurosecretory cell model, and release bioavailable Cu in cells. Furthermore, this shuttle has the capacity to protect cells in culture against oxidative stress-induced damage which occurs when Cu binds to the Aβ peptide. The aim of this study was therefore to characterize the cell entry route used by this shuttle and determine in which compartment Cu is released. Pharmacological treatments, siRNA silencing and colocalization experiments with GFP-Rab fusion proteins, indicate that the shuttle is internalized by an ATP-dependent endocytosis pathway involving both Rab5 and Rab14 endosomes route and suggest an early release of Cu from the shuttle.},
}

@article {pmid38645234,
year = {2024},
author = {Heavener, K and Kabra, K and Yidenk, M and Bradshaw, E},
title = {IL-1RA Disrupts ATP Activation of P2RX7 in Human Monocyte-Derived Microglia-like Cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.04.08.588607},
pmid = {38645234},
abstract = {The immune system has a dynamic role in neurodegenerative diseases, and purinergic receptors allow immune cells to recognize neuronal signaling, cell injury, or stress. Purinergic Receptor 7 (P2RX7) can modulate inflammatory cascades and its expression is upregulated in Alzheimer's disease (AD) brain tissue. P2RX7 expression is enriched in microglia, and elevated levels are found in microglia surrounding amyloid-beta plaques in the brain. While P2RX7 is thought to play a role in neurodegenerative diseases, how it modulates pathology and disease progression is not well understood. Here, we utilize a human monocyte-derived microglia-like cell (MDMi) model to interrogate P2RX7 activation and downstream consequences on microglia function. By using MDMi derived from human donors, we can examine how human donor variation impacts microglia function. We assessed P2RX7-driven IL1β and IL18 production and amyloid-beta peptide 1-42 (Aβ1-42) uptake levels. Our results show that ATP-stimulation of MDMi triggers upregulation of IL1β and IL18 expression. This upregulation of cytokine gene expression is blocked with the A740003 P2RX7 antagonist. We find that high extracellular ATP conditions also reduced MDMi capacity for Aβ1-42 uptake, and this loss of function is prevented through A740003 inhibition of P2RX7. In addition, pretreatment of MDMi with IL-1RA limited ATP-driven IL1β and IL18 gene expression upregulation, indicating that ATP immunomodulation of P2RX7 is IL-1R dependent. Aβ1-42 uptake was higher with IL-1RA pretreatment compared to ATP treatment alone, suggesting P2RX7 regulates phagocytic engulfment through IL-1 signaling. Overall, our results demonstrate that P2RX7 is a key response protein for high extracellular ATP in human microglia-like cells, and its function can be modulated by IL-1 signaling. This work opens the door to future studies examining anti-IL-1 biologics to increase the clearance of amyloid-beta.},
}

@article {pmid38644825,
year = {2024},
author = {Patil, N and Dhariwal, R and Mohammed, A and Wei, LS and Jain, M},
title = {Network pharmacology-based approach to elucidate the pharmacologic mechanisms of natural compounds from Dictyostelium discoideum for Alzheimer's disease treatment.},
journal = {Heliyon},
volume = {10},
number = {8},
pages = {e28852},
pmid = {38644825},
issn = {2405-8440},
abstract = {Alzheimer's disease (AD) is increasingly becoming a major public health concern in our society. While many studies have explored the use of natural polyketides, alkaloids, and other chemical components in AD treatment, there is an urgent need to clarify the concept of multi-target treatment for AD. This study focuses on using network pharmacology approach to elucidate how secondary metabolites from Dictyostelium discoideum affect AD through multi-target or indirect mechanisms. The secondary metabolites produced by D. discoideum during their development were obtained from literature sources and PubChem. Disease targets were selected using GeneCards, DisGeNET, and CTD databases, while compound-based targets were identified through Swiss target prediction and Venn diagrams were used to find intersections between these targets. A network depicting the interplay among disease, drugs, active ingredients, and key target proteins (PPI network) was formed utilizing the STRING (Protein-Protein Interaction Networks Functional Enrichment Analysis) database. To anticipate the function and mechanism of the screened compounds, GO and KEGG enrichment analyses were conducted and visually presented using graphs and bubble charts. After the screening phase, the top interacting targets in the PPI network and the compound with the most active target were chosen for subsequent molecular docking and molecular dynamic simulation studies. This study identified nearly 50 potential targeting genes for each of the screened compounds and revealed multiple signaling pathways. Among these pathways, the inflammatory pathway stood out. COX-2, a receptor associated with neuroinflammation, showed differential expression in various stages of AD, particularly in pyramidal neurons during the early stages of the disease. This increase in COX-2 expression is likely induce by higher levels of IL-1, which is associated with neuritic plaques and microglial cells in AD. Molecular docking investigations demonstrated a strong binding interaction between the terpene compound PQA-11 and the neuroinflammatory receptor COX2, with a substantial binding affinity of -8.4 kcal/mol. Subsequently, a thorough analysis of the docked complex (COX2-PQA11) through Molecular Dynamics Simulation showed lower RMSD, minimal RMSF fluctuations, and a reduced total energy of -291.35 kJ/mol compared to the standard drug. These findings suggest that the therapeutic effect of PQA-11 operates through the inflammatory pathway, laying the groundwork for further in-depth research into the role of secondary metabolites in AD treatment.},
}

@article {pmid38644711,
year = {2024},
author = {Shanaida, M and Lysiuk, R and Mykhailenko, O and Hudz, N and Abdulsalam, A and Gontova, T and Oleshchuk, O and Ivankiv, Y and Shanaida, V and Lytkin, D and Bjørklund, G},
title = {Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673300496240416114827},
pmid = {38644711},
issn = {1875-533X},
abstract = {The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.},
}

@article {pmid38644708,
year = {2024},
author = {Patwekar, M and Patwekar, F and Khan, S and Sharma, R and Kumar, D},
title = {Navigating the Alzheimer's Treatment Landscape: Unraveling Amyloid-Beta Complexities and Pioneering Precision Medicine Approaches.},
journal = {Current topics in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680266295495240415114919},
pmid = {38644708},
issn = {1873-4294},
abstract = {A variety of cutting-edge methods and good knowledge of the illness's complex causes are causing a sea change in the field of Alzheimer's Disease (A.D.) research and treatment. Precision medicine is at the vanguard of this change, where individualized treatment plans based on genetic and biomarker profiles give a ray of hope for customized therapeutics. Combination therapies are becoming increasingly popular as a way to address the multifaceted pathology of Alzheimer's by simultaneously attacking Aβ plaques, tau tangles, neuroinflammation, and other factors. The article covers several therapeutic design efforts, including BACE inhibitors, gamma- secretase modulators, monoclonal antibodies (e.g., Aducanumab and Lecanemab), and anti- Aβ vaccinations. While these techniques appear promising, clinical development faces safety concerns and uneven efficacy. To address the complicated Aβ pathology in Alzheimer's disease, a multimodal approach is necessary. The statement emphasizes the continued importance of clinical trials in addressing safety and efficacy concerns. Looking ahead, it suggests that future treatments may take into account genetic and biomarker traits in order to provide more personalized care. Therapies targeting Aβ, tau tangles, neuroinflammation, and novel drug delivery modalities are planned. Nanoparticles and gene therapies are only two examples of novel drug delivery methods that have the potential to deliver treatments more effectively, with fewer side effects, and with better therapeutic results. In addition, medicines that target tau proteins in addition to Aβ are in the works. Early intervention, based on precise biomarkers, is a linchpin of Alzheimer's care, emphasizing the critical need for detecting the disease at its earliest stages. Lifestyle interventions, encompassing diet, exercise, cognitive training, and social engagement, are emerging as key components in the fight against cognitive decline. Data analytics and art are gaining prominence as strategies to mitigate the brain's inflammatory responses. To pool knowledge and resources in the fight against Alzheimer's, international cooperation between scientists, doctors, and pharmaceutical companies is still essential. In essence, a complex, individualized, and collaborative strategy will characterize Alzheimer's research and therapy in the future. Despite obstacles, these encouraging possibilities show the ongoing commitment of the scientific and medical communities to combat A.D. head-on, providing a glimmer of hope to the countless people and families touched by this savage sickness.},
}

@article {pmid38644578,
year = {2024},
author = {Yao, Q and Long, C and Yi, P and Zhang, G and Wan, W and Rao, X and Ying, J and Liang, W and Hua, F},
title = {C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.},
journal = {CNS neuroscience & therapeutics},
volume = {30},
number = {4},
pages = {e14721},
pmid = {38644578},
issn = {1755-5949},
support = {jxsq2019201023//Jiangxi Province "Double Thousand Plan"/ ; 82060219//National Natural Science Foundation of China/ ; 82271234//National Natural Science Foundation of China/ ; 20212ACB216009//Natural Science Foundation of Jiangxi Province/ ; 20212BAB216048//Natural Science Foundation of Jiangxi Province/ ; 2019YNTD12003//Youth Team Project of the Second Affiliated Hospital of Nanchang University/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; *Disease Progression ; Animals ; Amyloid beta-Peptides/metabolism ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.

AIMS: Several studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.

METHODS: A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.

RESULTS: Overexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).

DISCUSSION: The correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).

CONCLUSION: The overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics
*Disease Progression
Animals
Amyloid beta-Peptides/metabolism

@article {pmid38643565,
year = {2024},
author = {Cai, Z and Yang, Z and Li, H and Fang, Y},
title = {Research progress of PROTACs for neurodegenerative diseases therapy.},
journal = {Bioorganic chemistry},
volume = {147},
number = {},
pages = {107386},
doi = {10.1016/j.bioorg.2024.107386},
pmid = {38643565},
issn = {1090-2120},
abstract = {Neurodegenerative diseases (NDD) are characterized by the gradual deterioration of neuronal function and integrity, resulting in an overall decline in brain function. The existing therapeutic options for NDD, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, fall short of meeting the clinical demand. A prominent pathological hallmark observed in numerous neurodegenerative disorders is the aggregation and misfolding of proteins both within and outside neurons. These abnormal proteins play a pivotal role in the pathogenesis of neurodegenerative diseases. Targeted degradation of irregular proteins offers a promising avenue for NDD treatment. Proteolysis-targeting chimeras (PROTACs) function via the ubiquitin-proteasome system and have emerged as a novel and efficacious approach in drug discovery. PROTACs can catalytically degrade "undruggable" proteins even at exceptionally low concentrations, allowing for precise quantitative control of aberrant protein levels. In this review, we present a compilation of reported PROTAC structures and their corresponding biological activities aimed at addressing NDD. Spanning from 2016 to present, this review provides an up-to-date overview of PROTAC-based therapeutic interventions. Currently, most protein degraders intended for NDD treatment remain in the preclinical research phase. Overcoming several challenges is imperative, including enhancing oral bioavailability and permeability across the blood-brain barrier, before these compounds can progress to clinical research or eventually reach the market. However, armed with an enhanced comprehension of the underlying pathological mechanisms and the emergence of innovative scaffolds for protein degraders, along with further structural optimization, we are confident that PROTAC possesses the potential to make substantial breakthroughs in the field of neurodegenerative diseases.},
}

@article {pmid38643562,
year = {2024},
author = {Sharma, V and Chander Sharma, P and Reang, J and Yadav, V and Kumar Tonk, R and Majeed, J and Sharma, K},
title = {Impact of GSK-3β and CK-1δ on Wnt signaling pathway in alzheimer disease: A dual target approach.},
journal = {Bioorganic chemistry},
volume = {147},
number = {},
pages = {107378},
doi = {10.1016/j.bioorg.2024.107378},
pmid = {38643562},
issn = {1090-2120},
abstract = {Alzheimer's disease (AD) is an enigmatic neurological illness that offers few treatment options. Recent exploration has highlighted the crucial connection of the Wnt signaling pathway in AD pathogenesis, shedding light on potential therapeutic targets. The present study focuses on the dual targeting of glycogen synthase kinase-3β (GSK-3β) and casein kinase-1δ (CK-1δ) within the framework of the Wnt signaling pathway as a possible technique for AD intervention. GSK-3β and CK-1δ are multifunctional kinases known for their roles in tau hyperphosphorylation, amyloid processing, and synaptic dysfunction, all of which are major hallmarks of Alzheimer's disease. They are intricately linked to Wnt signaling, which plays a pivotal part in sustaining neuronal function and synaptic plasticity. Dysregulation of the Wnt pathway in AD contributes to cognitive decline and neurodegeneration. This review delves into the molecular mechanisms by which GSK-3β and CK-1δ impact the Wnt signaling pathway, elucidating their roles in AD pathogenesis. We discuss the potential of small-molecule inhibitors along with their SAR studies along with the multi-targetd approach targeting GSK-3β and CK-1δ to modulate Wnt signaling and mitigate AD-related pathology. In summary, the dual targeting of GSK-3β and CK-1δ within the framework of the Wnt signaling pathway presents an innovative and promising avenue for future AD therapies, offering new hope for patients and caregivers in the quest to combat this challenging condition.},
}

@article {pmid38643230,
year = {2024},
author = {Jing, X and Wang, L and Song, M and Geng, H and Li, W and Huo, Y and Huang, A and Wang, X and An, C},
title = {Serum neurofilament light chain and inflammatory cytokines as biomarkers for early detection of mild cognitive impairment.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {9072},
pmid = {38643230},
issn = {2045-2322},
support = {ZF2024136//The government funded clinical medicine excellent talents training project of Hebei Province/ ; 199477138G//the Special Fund Project of the Central Government to Guide the Local Science and Technology Development of Hebei Province/ ; SG2021189//Science and Technology Program of Hebei Province/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Intermediate Filaments ; *Alzheimer Disease ; Neurofilament Proteins ; *Cognitive Dysfunction/diagnosis ; Biomarkers ; tau Proteins ; Amyloid beta-Peptides ; },
abstract = {To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, and the diagnostic performance of the cognitive assessment scales and serum biomarker concentrations was evaluated using receiver operating characteristic (ROC) curve analysis. Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1β, IL-6, and Aβ40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy. Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral serum biomarker for MCI detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.},
}

Humans
Cross-Sectional Studies
Intermediate Filaments
*Alzheimer Disease
Neurofilament Proteins
*Cognitive Dysfunction/diagnosis
Biomarkers
tau Proteins
Amyloid beta-Peptides

@article {pmid38642715,
year = {2024},
author = {Tong, B and Ba, Y and Li, Z and Yang, C and Su, K and Qi, H and Zhang, D and Liu, X and Wu, Y and Chen, Y and Ling, J and Zhang, J and Yu, P and Yin, X},
title = {Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {106505},
doi = {10.1016/j.nbd.2024.106505},
pmid = {38642715},
issn = {1095-953X},
abstract = {Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.},
}

@article {pmid38642702,
year = {2024},
author = {Cheng, J and Liang, T and Xie, XQ and Feng, Z and Meng, L},
title = {A new era of antibody discovery: an in-depth review of AI-driven approaches.},
journal = {Drug discovery today},
volume = {},
number = {},
pages = {103984},
doi = {10.1016/j.drudis.2024.103984},
pmid = {38642702},
issn = {1878-5832},
abstract = {Given their high affinity and specificity for a range of macromolecules, antibodies are widely used in the treatment of autoimmune diseases, cancers, inflammatory diseases, and Alzheimer's disease (AD). Traditional experimental methods are time-consuming, expensive, and labor-intensive. Recent advances in artificial intelligence (AI) technologies provide complementary methods that can reduce the time and costs required for antibody design by minimizing failures and increasing the success rate of experimental tests. In this review, we scrutinize the plethora of AI-driven methodologies that have been deployed over the past 4 years for modeling antibody structures, predicting antibody-antigen interactions, optimizing antibody affinity, and generating novel antibody candidates. We also briefly address the challenges faced in integrating AI-based models with traditional antibody discovery pipelines and highlight the potential future directions in this burgeoning field.},
}

@article {pmid38641599,
year = {2024},
author = {Ackmann, J and Brüge, A and Gotina, L and Lim, S and Jahreis, K and Vollbrecht, AL and Kim, YK and Pae, AN and Labus, J and Ponimaskin, E},
title = {Structural determinants for activation of the Tau kinase CDK5 by the serotonin receptor 5-HT7R.},
journal = {Cell communication and signaling : CCS},
volume = {22},
number = {1},
pages = {233},
pmid = {38641599},
issn = {1478-811X},
support = {StrucMed-Scholarship//Hannover Biomedical Research School - Graduate School of Excellence/ ; StrucMed-Scholarship//Hannover Biomedical Research School - Graduate School of Excellence/ ; StrucMed-Scholarship//Hannover Biomedical Research School - Graduate School of Excellence/ ; KSC-2022-CRE-0435//Korea Institute of Science and Technology Information (KISTI-HPC)/ ; KSC-2022-CRE-0435//Korea Institute of Science and Technology Information (KISTI-HPC)/ ; 2E32161//Korea Institute Science and Technology (KIST) institutional Program/ ; 2E32161//Korea Institute Science and Technology (KIST) institutional Program/ ; LA4465//Deutsche Forschungsgemeinschaft/ ; PO732//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Cyclin-Dependent Kinase 5/metabolism ; Phosphorylation ; *Alzheimer Disease/metabolism ; Signal Transduction ; Receptors, Serotonin/metabolism ; },
abstract = {BACKGROUND: Multiple neurodegenerative diseases are induced by the formation and deposition of protein aggregates. In particular, the microtubule-associated protein Tau leads to the development of so-called tauopathies characterized by the aggregation of hyperphosphorylated Tau within neurons. We recently showed that the constitutive activity of the serotonin receptor 7 (5-HT7R) is required for Tau hyperphosphorylation and aggregation through activation of the cyclin-dependent kinase 5 (CDK5). We also demonstrated physical interaction between 5-HT7R and CDK5 at the plasma membrane suggesting that the 5-HT7R/CDK5 complex is an integral part of the signaling network involved in Tau-mediated pathology.

METHODS: Using biochemical, microscopic, molecular biological, computational and AI-based approaches, we investigated structural requirements for the formation of 5-HT7R/CDK5 complex.

RESULTS: We demonstrated that 5-HT7R domains responsible for coupling to Gs proteins are not involved in receptor interaction with CDK5. We also created a structural model of the 5-HT7R/CDK5 complex and refined the interaction interface. The model predicted two conserved phenylalanine residues, F278 and F281, within the third intracellular loop of 5-HT7R to be potentially important for complex formation. While site-directed mutagenesis of these residues did not influence Gs protein-mediated receptor signaling, replacement of both phenylalanines by alanine residues significantly reduced 5-HT7R/CDK5 interaction and receptor-mediated CDK5 activation, leading to reduced Tau hyperphosphorylation and aggregation. Molecular dynamics simulations of 5-HT7R/CDK5 complex for wild-type and receptor mutants confirmed binding interface stability of the initial model.

CONCLUSIONS: Our results provide a structural basis for the development of novel drugs targeting the 5-HT7R/CDK5 interaction interface for the selective treatment of Tau-related disorders, including frontotemporal dementia and Alzheimer's disease.},
}

Humans
*Cyclin-Dependent Kinase 5/metabolism
Phosphorylation
*Alzheimer Disease/metabolism
Signal Transduction
Receptors, Serotonin/metabolism

@article {pmid38641585,
year = {2024},
author = {Hao, X and Abeysinghe, R and Zheng, F and Schulz, PE and , and Cui, L},
title = {Mapping of Alzheimer's disease related data elements and the NIH Common Data Elements.},
journal = {BMC medical informatics and decision making},
volume = {24},
number = {Suppl 3},
pages = {103},
pmid = {38641585},
issn = {1472-6947},
support = {R21AG068994/AG/NIA NIH HHS/United States ; R01NS116287/NS/NINDS NIH HHS/United States ; },
mesh = {United States/epidemiology ; Humans ; *Alzheimer Disease/diagnostic imaging/epidemiology ; Common Data Elements ; Neuroimaging ; National Institutes of Health (U.S.) ; },
abstract = {BACKGROUND: Alzheimer's Disease (AD) is a devastating disease that destroys memory and other cognitive functions. There has been an increasing research effort to prevent and treat AD. In the US, two major data sharing resources for AD research are the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI); Additionally, the National Institutes of Health (NIH) Common Data Elements (CDE) Repository has been developed to facilitate data sharing and improve the interoperability among data sets in various disease research areas.

METHOD: To better understand how AD-related data elements in these resources are interoperable with each other, we leverage different representation models to map data elements from different resources: NACC to ADNI, NACC to NIH CDE, and ADNI to NIH CDE. We explore bag-of-words based and word embeddings based models (Word2Vec and BioWordVec) to perform the data element mappings in these resources.

RESULTS: The data dictionaries downloaded on November 23, 2021 contain 1,195 data elements in NACC, 13,918 in ADNI, and 27,213 in NIH CDE Repository. Data element preprocessing reduced the numbers of NACC and ADNI data elements for mapping to 1,099 and 7,584 respectively. Manual evaluation of the mapping results showed that the bag-of-words based approach achieved the best precision, while the BioWordVec based approach attained the best recall. In total, the three approaches mapped 175 out of 1,099 (15.92%) NACC data elements to ADNI; 107 out of 1,099 (9.74%) NACC data elements to NIH CDE; and 171 out of 7,584 (2.25%) ADNI data elements to NIH CDE.

CONCLUSIONS: The bag-of-words based and word embeddings based approaches showed promise in mapping AD-related data elements between different resources. Although the mapping approaches need further improvement, our result indicates that there is a critical need to standardize CDEs across these valuable AD research resources in order to maximize the discoveries regarding AD pathophysiology, diagnosis, and treatment that can be gleaned from them.},
}

United States/epidemiology
Humans
*Alzheimer Disease/diagnostic imaging/epidemiology
Common Data Elements
Neuroimaging
National Institutes of Health (U.S.)

@article {pmid38640313,
year = {2024},
author = {Chen, Y and Lai, M and Tao, M},
title = {Evaluating the efficacy and safety of Alzheimer's disease drugs: A meta-analysis and systematic review.},
journal = {Medicine},
volume = {103},
number = {16},
pages = {e37799},
pmid = {38640313},
issn = {1536-5964},
mesh = {Humans ; *Alzheimer Disease/drug therapy/chemically induced ; Donepezil/therapeutic use ; Galantamine/therapeutic use ; Memantine/therapeutic use ; Molecular Docking Simulation ; Cholinesterase Inhibitors/therapeutic use ; Rivastigmine/therapeutic use ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.

OBJECTIVE: The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.

METHODS: We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.

RESULTS: All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.

CONCLUSION: ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.},
}

Humans
*Alzheimer Disease/drug therapy/chemically induced
Donepezil/therapeutic use
Galantamine/therapeutic use
Memantine/therapeutic use
Molecular Docking Simulation
Cholinesterase Inhibitors/therapeutic use
Rivastigmine/therapeutic use

@article {pmid38640161,
year = {2024},
author = {Zhang, Z and Lim, MJR},
title = {Incident Dementia After Spontaneous Intracerebral Hemorrhage.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-240111},
pmid = {38640161},
issn = {1875-8908},
abstract = {Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0-37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition.},
}

@article {pmid38640157,
year = {2024},
author = {Khaled, M and Al-Jamal, H and Tajer, L and El-Mir, R},
title = {Alzheimer's Disease in Lebanon: Exploring Genetic and Environmental Risk Factors-A Comprehensive Review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-231432},
pmid = {38640157},
issn = {1875-8908},
abstract = {Alzheimer's disease (AD) is a neurodegenerative condition that displays a high prevalence in Lebanon causing a local burden in healthcare and socio-economic sectors. Unfortunately, the lack of prevalence studies and clinical trials in Lebanon minimizes the improvement of AD patient health status. In this review, we include over 155 articles to cover the different aspects of AD ranging from mechanisms to possible treatment and management tools. We highlight some important modifiable and non-modifiable risk factors of the disease including genetics, age, cardiovascular diseases, smoking, etc. Finally, we propose a hypothetical genetic synergy model between APOE4 and TREM2 genes which constitutes a potential early diagnostic tool that helps in reducing the risk of AD based on preventative measures decades before cognitive decline. The studies on AD in Lebanon and the Middle East are scarce. This review points out the importance of genetic mapping in the understanding of disease pathology which is crucial for the emergence of novel diagnostic tools. Hence, we establish a rigid basis for further research to identify the most influential genetic and environmental risk factors for the purpose of using more specific diagnostic tools and possibly adopting a local management protocol.},
}

@article {pmid38639864,
year = {2024},
author = {Rahimi, A and Sameei, P and Mousavi, S and Ghaderi, K and Hassani, A and Hassani, S and Alipour, S},
title = {Application of CRISPR/Cas9 System in the Treatment of Alzheimer's Disease and Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {38639864},
issn = {1559-1182},
abstract = {Alzheimer's, Parkinson's, and Huntington's are some of the most common neurological disorders, which affect millions of people worldwide. Although there have been many treatments for these diseases, there are still no effective treatments to treat or completely stop these disorders. Perhaps the lack of proper treatment for these diseases can be related to various reasons, but the poor results related to recent clinical research also prompted doctors to look for new treatment approaches. In this regard, various researchers from all over the world have provided many new treatments, one of which is CRISPR/Cas9. Today, the CRISPR/Cas9 system is mostly used for genetic modifications in various species. In addition, by using the abilities available in the CRISPR/Cas9 system, researchers can either remove or modify DNA sequences, which in this way can establish a suitable and useful treatment method for the treatment of genetic diseases that have undergone mutations. We conducted a non-systematic review of articles and study results from various databases, including PubMed, Medline, Web of Science, and Scopus, in recent years. and have investigated new treatment methods in neurodegenerative diseases with a focus on Alzheimer's disease. Then, in the following sections, the treatment methods were classified into three groups: anti-tau, anti-amyloid, and anti-APOE regimens. Finally, we discussed various applications of the CRISPR/Cas-9 system in Alzheimer's disease. Today, using CRISPR/Cas-9 technology, scientists create Alzheimer's disease models that have a more realistic phenotype and reveal the processes of pathogenesis; following the screening of defective genes, they establish treatments for this disease.},
}

@article {pmid38638958,
year = {2024},
author = {Wu, J and Chen, J and Ge, Y and Huang, N and Luo, Y},
title = {Neuroprotective effect of tanshinone IIA-modified mesenchymal stem cells in a lipopolysaccharide-induced neuroinflammation model.},
journal = {Heliyon},
volume = {10},
number = {8},
pages = {e29424},
pmid = {38638958},
issn = {2405-8440},
abstract = {In this study, the neuroprotective potential of tanshinone IIA (TIIA)-modified mesenchymal stem cells (MSC) were investigated using a murine model of lipopolysaccharide (LPS)-induced neuroinflammation. The cognitive performance of the mice was assessed using the Y-maze and Morris water maze tests, while immunofluorescence and Western blot analyses were employed to evaluate the hippocampal expression of pertinent markers and inflammatory factors, respectively. The results from the behavioral experiments demonstrated discernible differences in learning and memory abilities between the model group and the control group (P < 0.05), confirming the successful induction of neuroinflammation. Both the MSC and TIIA-MSC groups exhibited enhancements in the cognitive abilities of neuroinflammatory mice, with the TIIA-MSC group demonstrating a more pronounced improvement (P < 0.01). Immunofluorescence analysis revealed significant activation of microglia in the model group, while the MSC and TIIA-MSC groups exhibited a reduction in hippocampal microglial activation, with the TIIA-MSC group displaying a more substantial decrease. A statistically significant difference in the expression levels of IL-1, IL-6, and TNF-α was observed between the model and control groups (P < 0.05), indicating that IL-1, IL-6, and TNF-α were downregulated in both the MSC and TIIA-MSC groups. Notably, the downregulatory effect was more prominent in the TIIA-MSC group (P < 0.01). Compared to MSC treatment alone, the administration of TIIA-modified MSC demonstrated a superior protective effect against lipopolysaccharide-induced neuroinflammation. These findings underscore the potential therapeutic efficacy of TIIA-modified MSC in mitigating neuroinflammatory responses.},
}

@article {pmid38638932,
year = {2024},
author = {Yan, F and Yang, M and Sun, Y and Tang, Q and Yuan, L},
title = {Case report: Methicillin-resistant Staphylococcus aureus with penicillin susceptible (PS-MRSA): first clinical report from a psychiatric hospital in China.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1380369},
pmid = {38638932},
issn = {2296-858X},
abstract = {This case report documents the first instance of Penicillin-Susceptible Methicillin-Resistant Staphylococcus aureus (PS-MRSA) in a Chinese psychiatric hospital. The strain was isolated from a patient with Alzheimer's disease who had a lower respiratory tract infection. Clinical and laboratory analyses, including mass spectrometry, antibiotic susceptibility testing, and whole-genome sequencing, confirmed the PS-MRSA strain. In this case, we systematically introduce the clinical symptoms, laboratory findings, and treatment responses associated with this PS-MRSA strain. This discovery offers a new perspective on our understanding of resistance mechanisms and expands our considerations for existing antibiotic treatments. It may fill a gap in the classification of MRSA strains, enhance the spectrum of MRSA resistance, and complete the therapeutic strategies for MRSA.},
}

@article {pmid38638303,
year = {2024},
author = {Jiang, S and Sydney, EJ and Runyan, AM and Serpe, R and Srikanth, M and Figueroa, HY and Yang, M and Myeku, N},
title = {5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1338502},
pmid = {38638303},
issn = {1662-5102},
abstract = {BACKGROUND: Accumulation of tau in synapses in the early stages of Alzheimer's disease (AD) has been shown to cause synaptic damage, synaptic loss, and the spread of tau pathology through trans-synaptically connected neurons. Moreover, synaptic loss correlates with a decline in cognitive function, providing an opportunity to investigate therapeutic strategies to target synapses and synaptic tau to rescue or prevent cognitive decline in AD. One of the promising synaptic targets is the 5-HT4 serotonergic receptor present postsynaptically in the brain structures involved in the memory processes. 5-HT4R stimulation exerts synaptogenic and pro-cognitive effects involving synapse-to-nucleus signaling essential for synaptic plasticity. However, it is not known whether 5-HT4R activation has a therapeutic effect on tau pathology.

METHODS: The goal of this study was to investigate the impact of chronic stimulation of 5-HT4R by two agonists, prucalopride and RS-67333, in PS19 mice, a model of tauopathy. We utilized gradient assays to isolate pre- and post-synaptic compartments, followed by biochemical analyses for tau species and ubiquitinated proteins in the synaptic compartments and total brain tissue. Next, we performed kinetic assays to test the proteasome's hydrolysis capacity in treatment conditions. Moreover, behavioral tests such as the open field and non-maternal nest-building tests were used to evaluate anxiety-like behaviors and hippocampal-related cognitive functioning in the treatment paradigm.

RESULTS: Our results show that 5-HT4R agonism reduced tauopathy, reduced synaptic tau, increased proteasome activity, and improved cognitive functioning in PS19 mice. Our data suggest that enhanced proteasome activity by synaptic mediated signaling leads to the enhanced turnover of tau initially within synapses where the receptors are localized, and over time, the treatment attenuated the accumulation of tau aggregation and improved cognitive functioning of the PS19 mice.

CONCLUSION: Therefore, stimulation of 5-HT4R offers a promising therapy to rescue synapses from the accumulation of toxic synaptic tau, evident in the early stages of AD.},
}

@article {pmid38636309,
year = {2024},
author = {Durham, PG and Butnariu, A and Alghorazi, R and Pinton, G and Krishna, V and Dayton, PA},
title = {Current clinical investigations of focused ultrasound blood-brain barrier disruption: A review.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {21},
number = {3},
pages = {e00352},
doi = {10.1016/j.neurot.2024.e00352},
pmid = {38636309},
issn = {1878-7479},
abstract = {The blood-brain barrier (BBB) presents a formidable challenge in delivering therapeutic agents to the central nervous system. Ultrasound-mediated BBB disruption has emerged as a promising non-invasive technique to enhance drug delivery to the brain. This manuscript reviews fundamental principles of ultrasound-based techniques and their mechanisms of action in temporarily permeabilizing the BBB. Clinical trials employing ultrasound for BBB disruption are discussed, summarizing diverse applications ranging from the treatment of neurodegenerative diseases to targeted drug delivery for brain tumors. The review also addresses safety considerations, outlining the current understanding of potential risks and mitigation strategies associated with ultrasound exposure, including real-time monitoring and assessment of treatment efficacy. Among the large number of studies, significant successes are highlighted thus providing perspective on the future direction of the field.},
}

@article {pmid38634567,
year = {2024},
author = {Chai, B and Wu, Y and Yang, H and Fan, B and Cao, S and Zhang, X and Xie, Y and Hu, Z and Ma, Z and Zhang, Y and Pan, W and Meng, W and Meng, J and Tian, W and Zhang, J and Li, Y and Shao, Y and Wang, S},
title = {Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e2310134},
doi = {10.1002/advs.202310134},
pmid = {38634567},
issn = {2198-3844},
support = {82260577//National Natural Science Foundation of China/ ; 82002726//National Natural Science Foundation of China/ ; 82203714//National Natural Science Foundation of China/ ; 82002758//National Natural Science Foundation of China/ ; H-2019007//Yunnan Provincial Medical Reserve Talents Project/ ; CZ0165//Young and Middle-aged Reserve Academic and Technical Leaders in Yunnan Province/ ; },
abstract = {Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14-3-3 and ultimately forming the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO-dependent ferroptosis. In vivo, treatment with ferrostatin-1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease- or Parkinson's disease-related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex is LPO-dependent rather than GPX4-dependent is hypothesized.},
}

@article {pmid38634361,
year = {2024},
author = {Andrade, SM and de Oliveira Marques, CC and de Lucena, LC and Vieira da Costa, K and de Souza, IC and da Silva Machado, CB and Queiroz, MEBS and Costa, LP and Silva, STD},
title = {Effect of transcranial direct current stimulation and transcranial magnetic stimulation on the cognitive function of individuals with Alzheimer's disease: a systematic review with meta-analysis and meta-regression.},
journal = {Neurological research},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/01616412.2024.2321779},
pmid = {38634361},
issn = {1743-1328},
abstract = {OBJECTIVE: To analyze the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) on the cognitive function of individuals with Alzheimer's disease (AD).

METHODS: This systematic review with meta-analysis and meta-regression included randomized clinical trials published until 05/2022. We included studies conducted with individuals with AD of both sexes, aged between 55 and 85 years, treated with tDCS, TMS, or both.

RESULTS: Twenty-one studies were included in the systematic review and sixteen in the meta-analysis. Meta-regression suggested a significant influence of anodic tDCS with current intensity of 1.5 mA on cognitive function. Significant results were found with treatment frequencies of three and five days a week for two weeks. Subgroup analysis found that anodic tDCS influences cognitive function, regardless of AD stage. Similar was observed for TMS using a frequency of 20 Hz and current intensity of 90% of the resting motor threshold.

DISCUSSION: Anodal tDCS and 20 Hz TMS have demonstrated the ability to improve cognitive function in AD by modulating neural activity. These therapies are safe and well-tolerated, offering promise as adjuncts to available pharmacological treatments. Studies with greater methodological rigor and parameter standardization are warranted. Comprehensive investigations involving neuroimaging techniques may provide a better understanding of the interaction between induced electrical fields and the complex neural networks affected in AD, paving the way for more personalized and effective neurostimulation approaches.},
}

@article {pmid38634273,
year = {2024},
author = {Akkaya, D and Seyhan, G and Sari, S and Barut, B},
title = {In vitro and in silico investigation of FDA-approved drugs to be repurposed against Alzheimer's disease.},
journal = {Drug development research},
volume = {85},
number = {3},
pages = {e22184},
doi = {10.1002/ddr.22184},
pmid = {38634273},
issn = {1098-2299},
mesh = {Humans ; *Alzheimer Disease/drug therapy ; Acetylcholinesterase/metabolism ; *Trimebutine/therapeutic use ; Cholinesterase Inhibitors/chemistry ; Models, Molecular ; Molecular Docking Simulation ; },
abstract = {Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD.},
}

Humans
*Alzheimer Disease/drug therapy
Acetylcholinesterase/metabolism
*Trimebutine/therapeutic use
Cholinesterase Inhibitors/chemistry
Models, Molecular
Molecular Docking Simulation

@article {pmid38632621,
year = {2024},
author = {Liu, J and Wu, H and Robertson, DH and Zhang, J},
title = {Text mining and portal development for gene-specific publications on Alzheimer's disease and other neurodegenerative diseases.},
journal = {BMC medical informatics and decision making},
volume = {24},
number = {Suppl 3},
pages = {98},
pmid = {38632621},
issn = {1472-6947},
support = {U54 AG065181/AG/NIA NIH HHS/United States ; 5U54AG065181-02/NH/NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Alzheimer Disease ; *Neurodegenerative Diseases ; Data Mining/methods ; PubMed ; Databases, Factual ; },
abstract = {BACKGROUND: Tremendous research efforts have been made in the Alzheimer's disease (AD) field to understand the disease etiology, progression and discover treatments for AD. Many mechanistic hypotheses, therapeutic targets and treatment strategies have been proposed in the last few decades. Reviewing previous work and staying current on this ever-growing body of AD publications is an essential yet difficult task for AD researchers.

METHODS: In this study, we designed and implemented a natural language processing (NLP) pipeline to extract gene-specific neurodegenerative disease (ND) -focused information from the PubMed database. The collected publication information was filtered and cleaned to construct AD-related gene-specific publication profiles. Six categories of AD-related information are extracted from the processed publication data: publication trend by year, dementia type occurrence, brain region occurrence, mouse model information, keywords occurrence, and co-occurring genes. A user-friendly web portal is then developed using Django framework to provide gene query functions and data visualizations for the generalized and summarized publication information.

RESULTS: By implementing the NLP pipeline, we extracted gene-specific ND-related publication information from the abstracts of the publications in the PubMed database. The results are summarized and visualized through an interactive web query portal. Multiple visualization windows display the ND publication trends, mouse models used, dementia types, involved brain regions, keywords to major AD-related biological processes, and co-occurring genes. Direct links to PubMed sites are provided for all recorded publications on the query result page of the web portal.

CONCLUSION: The resulting portal is a valuable tool and data source for quick querying and displaying AD publications tailored to users' interested research areas and gene targets, which is especially convenient for users without informatic mining skills. Our study will not only keep AD field researchers updated with the progress of AD research, assist them in conducting preliminary examinations efficiently, but also offers additional support for hypothesis generation and validation which will contribute significantly to the communication, dissemination, and progress of AD research.},
}

Animals
Mice
*Alzheimer Disease
*Neurodegenerative Diseases
Data Mining/methods
PubMed
Databases, Factual

@article {pmid38631571,
year = {2024},
author = {Yang, J and Liao, Y and Cao, C and Yu, Q and Zhang, D and Yan, C},
title = {Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {131593},
doi = {10.1016/j.ijbiomac.2024.131593},
pmid = {38631571},
issn = {1879-0003},
abstract = {Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-β-D-Galp-(1 → and →4)-β-D-Glcp-(1 → residues substituted at the 4-position to the →4)-α-D-GalAp-(1 → residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2, nitric oxide synthase, TNF-α, IL-6, and interleukin-1β in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.},
}

@article {pmid38630416,
year = {2024},
author = {Furneri, G and Varrasi, S and Guerrera, CS and Platania, GA and Torre, V and Boccaccio, FM and Testa, MF and Martelli, F and Privitera, A and Razza, G and Santagati, M and Di Nuovo, S and Pirrone, C and Castellano, S and Caraci, F and Monastero, R},
title = {Combining Mini-Mental State Examination and Montreal Cognitive Assessment for assessing the clinical efficacy of cholinesterase inhibitors in mild Alzheimer's disease: a pilot study.},
journal = {Aging clinical and experimental research},
volume = {36},
number = {1},
pages = {95},
pmid = {38630416},
issn = {1720-8319},
mesh = {Humans ; *Cholinesterase Inhibitors/therapeutic use ; Pilot Projects ; *Alzheimer Disease/drug therapy ; Mental Status and Dementia Tests ; Treatment Outcome ; },
abstract = {Current drugs for Alzheimer's Disease (AD), such as cholinesterase inhibitors (ChEIs), exert only symptomatic activity. Different psychometric tools are needed to assess cognitive and non-cognitive dimensions during pharmacological treatment. In this pilot study, we monitored 33 mild-AD patients treated with ChEIs. Specifically, we evaluated the effects of 6 months (Group 1 = 17 patients) and 9 months (Group 2 = 16 patients) of ChEIs administration on cognition with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Frontal Assessment Battery (FAB), while depressive symptoms were measured with the Hamilton Depression Rating Scale (HDRS). After 6 months (Group 1), a significant decrease in MoCA performance was detected. After 9 months (Group 2), a significant decrease in MMSE, MoCA, and FAB performance was observed. ChEIs did not modify depressive symptoms. Overall, our data suggest MoCA is a potentially useful tool for evaluating the effectiveness of ChEIs.},
}

Humans
*Cholinesterase Inhibitors/therapeutic use
Pilot Projects
*Alzheimer Disease/drug therapy
Mental Status and Dementia Tests
Treatment Outcome

@article {pmid38630202,
year = {2024},
author = {Dai, M and Guo, Z and Xia, H and Zhu, H and Li, J and Hou, H and Zhao, G and Liu, X},
title = {Predicting the efficacy of donepezil intervention in Alzheimer's disease patients using regional homogeneity in the inferior orbitofrontal cortex.},
journal = {Aging clinical and experimental research},
volume = {36},
number = {1},
pages = {94},
pmid = {38630202},
issn = {1720-8319},
support = {2017KY109//by the General Project of the Department of Science and Technology of Zhejiang Province/ ; },
mesh = {Humans ; Donepezil/therapeutic use ; *Alzheimer Disease/diagnostic imaging/drug therapy ; Prefrontal Cortex/diagnostic imaging ; Brain ; Cognition ; },
abstract = {BACKGROUND: Although donepezil is a commonly used drug for treating Alzheimer's disease (AD), the mechanisms by which it affects patients' functional brain activity, and thus modulates clinical symptoms, remain unclear.

METHODS: In the present study, we used resting-state functional magnetic resonance imaging (MRI) and regional homogeneity (ReHo) to investigate the effects of donepezil on local brain activity in AD patients. Resting-state functional MRI data were collected from 32 subjects: 16 healthy controls and 16 AD patients. All 16 AD patients underwent 6 months of donepezil treatment and received two MRI scans (pre- and post-intervention). Analysis of covariance and post hoc analyses were used to compare ReHo differences among the healthy controls, pre-intervention AD patients, and post-intervention AD patients. Pearson correlation analysis was used to examine relationships between ReHo values in differential brain regions and clinical symptoms.

RESULTS: Compared with healthy controls, post-intervention AD patients had reduced ReHo in the orbital part of the inferior frontal gyrus, and pre-intervention AD patients had reduced ReHo in the orbital part of the right inferior frontal gyrus. Pattern recognition models revealed that pre-intervention ReHo values in abnormal brain regions of AD patients were 76% accurate for predicting the efficacy of donepezil on cognitive function and 65% accurate for predicting its efficacy on depressive symptoms.

CONCLUSIONS: These findings deepen our understanding of the brain mechanisms underlying the clinical efficacy of donepezil in AD patients, and provide a novel way to predict its clinical efficacy in such patients.},
}

Humans
Donepezil/therapeutic use
*Alzheimer Disease/diagnostic imaging/drug therapy
Prefrontal Cortex/diagnostic imaging
Brain
Cognition

@article {pmid38630163,
year = {2024},
author = {Perneczky, R and , and Nitschmann, S},
title = {[The monoclonal antibody gantenerumab in the treatment of early Alzheimer's disease].},
journal = {Innere Medizin (Heidelberg, Germany)},
volume = {},
number = {},
pages = {},
pmid = {38630163},
issn = {2731-7099},
}

@article {pmid38630150,
year = {2024},
author = {Yun, Q and Ma, SF and Zhang, WN and Gu, M and Wang, J},
title = {FoxG1 as a Potential Therapeutic Target for Alzheimer's Disease: Modulating NLRP3 Inflammasome via AMPK/mTOR Autophagy Pathway.},
journal = {Cellular and molecular neurobiology},
volume = {44},
number = {1},
pages = {35},
pmid = {38630150},
issn = {1573-6830},
support = {CJ20230082//Applied Basic Research Project of Changzhou/ ; xz202204//Station level project of Changzhou Blood Center/ ; BE2022782//Clinic Development Fund of Jiangsu Province/ ; },
mesh = {Animals ; Mice ; *Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; *Alzheimer Disease ; AMP-Activated Protein Kinases ; Neuroinflammatory Diseases ; Autophagy ; RNA, Small Interfering ; },
abstract = {An increasing body of research suggests that promoting microglial autophagy hinders the neuroinflammation initiated though the NLRP3 inflammasome activation in Alzheimer's disease (AD). The function of FoxG1, a crucial transcription factor involved in cell survival by regulating mitochondrial function, remains unknown during the AD process and neuroinflammation occurs. In the present study, we firstly found that Aβ peptides induced AD-like neuroinflammation upregulation and downregulated the level of autophagy. Following low-dose Aβ25-35 stimulation, FoxG1 expression and autophagy exhibited a gradual increase. Nevertheless, with high-concentration Aβ25-35 treatment, progressive decrease in FoxG1 expression and autophagy levels as the concentration of Aβ25-35 escalated. In addition, FoxG1 has a positive effect on cell viability and autophagy in the nervous system. In parallel with the Aβ25-35 stimulation, we employed siRNA to decrease the expression of FoxG1 in N2A cells. A substantial reduction in autophagy level (Beclin1, LC3II, SQSTM1/P62) and a notable growth in inflammatory response (NLRP3, TNF-α, and IL-6) were observed. In addition, we found FoxG1 overexpression owned the effect on the activation of AMPK/mTOR autophagy pathway and siRNA-FoxG1 successfully abolished this effect. Lastly, FoxG1 suppressed the NLRP3 inflammasome and enhanced the cognitive function in AD-like mouse model induced by Aβ25-35. Confirmed by cellular and animal experiments, FoxG1 suppressed NLRP3-mediated neuroinflammation, which was strongly linked to autophagy regulated by AMPK/mTOR. Taken together, FoxG1 may be a critical node in the pathologic progression of AD and has the potential to serve as therapeutic target.},
}

Animals
Mice
*Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
*Alzheimer Disease
AMP-Activated Protein Kinases
Neuroinflammatory Diseases
Autophagy
RNA, Small Interfering

@article {pmid38633542,
year = {2022},
author = {Akgül, F and Sevim, B and Arslan, Y and Şencan, M and Atabey, P and Aktaş, A},
title = {Predictors of Severity and Mortality in COVID-19: A Retrospective Study from Batman, Turkey.},
journal = {Infectious diseases & clinical microbiology},
volume = {4},
number = {1},
pages = {18-29},
pmid = {38633542},
issn = {2667-646X},
abstract = {OBJECTIVE: It is increasingly important to identify risk factors for COVID-19-associated mortality to provide access to early treatment. This study aimed to investigate the relationship between COVID-19 severity and laboratory data and demographic characteristics of hospitalized patients and to identify factors predicting mortality in COVID-19.

MATERIALS AND METHODS: The study is a retrospective and single-center study. Data of 1298 COVID-19 patients confirmed by a positive real-time polymerase chain reaction test for COVID-19 and treated at the hospital were retrospectively analyzed. Study patients were divided into three groups based on the clinical severity of disease: the mild-moderate group (n:954) and the severe (n:310) and critical (n:34) groups. Demographic characteristics, underlying diseases, and laboratory findings were compared between groups.

RESULTS: Multivariate logistic and ordinal logistic regression analysis revealed that male gender, old age, diabetes mellitus, coronary artery disease, cerebrovascular event, malignancy, chronic obstructive pulmonary disease, chronic renal failure, chronic hepatitis B, and Alzheimer's disease/dementia/Parkinson's disease (among neurological diseases) were independently associated with and significantly increased the development of severe disease and mortality.

CONCLUSION: The COVID-19 pandemic continues to be a significant health problem affecting all of humanity. Determining risk factors for COVID-19 severity and mortality are critical for classifying critical cases at the time of initial diagnosis, establishing appropriately specific treatment protocols, and ensuring access to early treatment.},
}

@article {pmid38629411,
year = {2024},
author = {Wirth, S and Schlößer, A and Beiersdorfer, A and Schweizer, M and Woo, MS and Friese, MA and Lohr, C and Grochowska, KM},
title = {Astrocytic uptake of posttranslationally modified amyloid-β leads to endolysosomal system disruption and induction of pro-inflammatory signaling.},
journal = {Glia},
volume = {},
number = {},
pages = {},
doi = {10.1002/glia.24539},
pmid = {38629411},
issn = {1098-1136},
support = {CRC 1436 TPA02//Deutsche Forschungsgemeinschaft/ ; SFB 1328 project number 335447717//Deutsche Forschungsgemeinschaft/ ; DE-20057p//Alzheimer Forschung Initiative/ ; },
abstract = {The disruption of astrocytic catabolic processes contributes to the impairment of amyloid-β (Aβ) clearance, neuroinflammatory signaling, and the loss of synaptic contacts in late-onset Alzheimer's disease (AD). While it is known that the posttranslational modifications of Aβ have significant implications on biophysical properties of the peptides, their consequences for clearance impairment are not well understood. It was previously shown that N-terminally pyroglutamylated Aβ3(pE)-42, a significant constituent of amyloid plaques, is efficiently taken up by astrocytes, leading to the release of pro-inflammatory cytokine tumor necrosis factor α and synapse loss. Here we report that Aβ3(pE)-42, but not Aβ1-42, gradually accumulates within the astrocytic endolysosomal system, disrupting this catabolic pathway and inducing the formation of heteromorphous vacuoles. This accumulation alters lysosomal kinetics, lysosome-dependent calcium signaling, and upregulates the lysosomal stress response. These changes correlate with the upregulation of glial fibrillary acidic protein (GFAP) and increased activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Treatment with a lysosomal protease inhibitor, E-64, rescues GFAP upregulation, NF-κB activation, and synapse loss, indicating that abnormal lysosomal protease activity is upstream of pro-inflammatory signaling and related synapse loss. Collectively, our data suggest that Aβ3(pE)-42-induced disruption of the astrocytic endolysosomal system leads to cytoplasmic leakage of lysosomal proteases, promoting pro-inflammatory signaling and synapse loss, hallmarks of AD-pathology.},
}

@article {pmid38629395,
year = {2024},
author = {Liu, Y and Li, X and Liu, S and Liang, T and Wu, Y and Wang, X and Li, Y and Xu, Y},
title = {Study on Gamma sensory flicker for Insomnia.},
journal = {The International journal of neuroscience},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/00207454.2024.2342974},
pmid = {38629395},
issn = {1563-5279},
abstract = {OBJECTIVES: Insomnia has been the subject of much systematic research because it is a risk factor for a variety of diseases. There is some evidence that gamma sensory stimulation therapy has also been demonstrated to improve sleep quality for people with Alzheimer's disease. However, it is unclear whether this method is effective for treating insomnia. The principal objective of this project was to investigate the efficacy and safety of gamma sensory flicker in improving the sleep quality of insomnia patients.

METHODS: Thirty-seven participants with insomnia were recruited for this prospective observational study. For a duration of 8 weeks, participants were exposed to flicker stimulation through a light and sound device.

RESULTS: During the main phase of the study, adherence rates averaged 92.21%. Additionally, no severe adverse events were reported for flicker treatment. Analysis of sleep diaries indicated that 40 Hz flickers can enhance sleep quality by reducing sleep onset latencies, and arousals, and increasing total sleep duration.

CONCLUSIONS: Gamma sensory flicker improves sleep quality in people suffering from insomnia.},
}

@article {pmid38628727,
year = {2024},
author = {Zou, C and Yang, T and Huang, X and Ren, X and Yang, C and Xu, B and Liu, J},
title = {Inhibition of autophagosome-lysosome fusion contributes to TDCIPP-induced Aβ1-42 production in N2a-APPswe cells.},
journal = {Heliyon},
volume = {10},
number = {8},
pages = {e26832},
pmid = {38628727},
issn = {2405-8440},
abstract = {Alzheimer's disease is the most common form of dementia and is characterized by cognitive impairment. The disruption of autophagosome-lysosome function has been linked to the pathogenesis of Alzheimer's disease. Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardant that has the potential to cause neuronal damage. We found that TDCIPP significantly increased the expression of β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), presenilin-1 (PS1) and Aβ42. Proteomic studies with TMT labeling revealed changes in the profiles of N2a-APPswe cells after exposure to TDCIPP. Proteomic and bioinformatics analyses revealed that lysosomal proteins were dysregulated in N2a-APPswe cells after treatment with TDCIPP. The LC3, P62, CTSD, and LAMP1 levels were increased after TDCIPP exposure, and dysregulated protein expression was validated by Western blotting. The exposure to TDCIPP led to the accumulation of autophagosomes, and this phenomenon was enhanced in the presence of chloroquine (CQ). Our results revealed for the first time that TDCIPP could be a potential environmental risk factor for AD development. The inhibition of autophagosome-lysosome fusion may have a significant impact on the generation of Aβ1-42 in response to TDCIPP.},
}

@article {pmid38628697,
year = {2024},
author = {Wang, H and Shi, L and Luo, S and Luo, Y and Xu, C and Qiu, G and Guo, Q and Chen, C and Lu, T and Liu, K and Zhu, F},
title = {Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1345705},
pmid = {38628697},
issn = {1664-2295},
abstract = {INTRODUCTION: The ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer's disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.

METHODS: Fourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann-Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.

RESULTS: Regarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.

CONCLUSION: APOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.},
}

@article {pmid38628595,
year = {2024},
author = {Qiu, C and Li, Z and Leigh, DA and Duan, B and Stucky, JE and Kim, N and Xie, G and Lu, KP and Zhou, XZ},
title = {The role of the Pin1-cis P-tau axis in the development and treatment of vascular contribution to cognitive impairment and dementia and preeclampsia.},
journal = {Frontiers in cell and developmental biology},
volume = {12},
number = {},
pages = {1343962},
pmid = {38628595},
issn = {2296-634X},
abstract = {Tauopathies are neurodegenerative diseases characterized by deposits of abnormal Tau protein in the brain. Conventional tauopathies are often defined by a limited number of Tau epitopes, notably neurofibrillary tangles, but emerging evidence suggests structural heterogeneity among tauopathies. The prolyl isomerase Pin1 isomerizes cis P-tau to inhibit the development of oligomers, tangles and neurodegeneration in multiple neurodegenerative diseases such as Alzheimer's disease, traumatic brain injury, vascular contribution to cognitive impairment and dementia (VCID) and preeclampsia (PE). Thus, cis P-tau has emerged as an early etiological driver, blood marker and therapeutic target for multiple neurodegenerative diseases, with clinical trials ongoing. The discovery of cis P-tau and other tau pathologies in VCID and PE calls attention for simplistic classification of tauopathy in neurodegenerative diseases. These recent advances have revealed the exciting novel role of the Pin1-cis P-tau axis in the development and treatment of vascular contribution to cognitive impairment and dementia and preeclampsia.},
}

@article {pmid38627829,
year = {2024},
author = {Luo, YX and Yang, LL and Yao, XQ},
title = {Gut microbiota-host lipid crosstalk in Alzheimer's disease: implications for disease progression and therapeutics.},
journal = {Molecular neurodegeneration},
volume = {19},
number = {1},
pages = {35},
pmid = {38627829},
issn = {1750-1326},
support = {No.82371427//National Natural Science Foundation of China/ ; CSTB2023NSCQBHX0018//Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission/ ; CSTB2023NSCQ-MSX0323//Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission/ ; No. kryc-lj-2105//Chongqing Medical University/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism ; *Gastrointestinal Microbiome/physiology ; Lipid Metabolism ; Disease Progression ; Lipids ; },
abstract = {Trillions of intestinal bacteria in the human body undergo dynamic transformations in response to physiological and pathological changes. Alterations in their composition and metabolites collectively contribute to the progression of Alzheimer's disease. The role of gut microbiota in Alzheimer's disease is diverse and complex, evidence suggests lipid metabolism may be one of the potential pathways. However, the mechanisms that gut microbiota mediate lipid metabolism in Alzheimer's disease pathology remain unclear, necessitating further investigation for clarification. This review highlights the current understanding of how gut microbiota disrupts lipid metabolism and discusses the implications of these discoveries in guiding strategies for the prevention or treatment of Alzheimer's disease based on existing data.},
}

Humans
*Alzheimer Disease/metabolism
*Gastrointestinal Microbiome/physiology
Lipid Metabolism
Disease Progression
Lipids

@article {pmid38626288,
year = {2024},
author = {Borikar, SP and Sonawane, DS and Tapre, DN and Jain, SP},
title = {Exploring the neuropharmacological potential of empagliflozin on nootropic and scopolamine-induced amnesic model of Alzheimer's like conditions in rats.},
journal = {The International journal of neuroscience},
volume = {},
number = {},
pages = {1-28},
doi = {10.1080/00207454.2024.2342973},
pmid = {38626288},
issn = {1563-5279},
abstract = {Alzheimer disease (AD) is one of the most challenging and prevalent neurodegenerative disorder globally with a rising prevalence, characterized by progressive cognitive decline, memory loss, and behavioural changes. Current research aims to determine the nootropic and anti-amnesic effect of Empagliflozin (EMPA) against scopolamine-induced amnesia in rats, by modulating the cholinergic and N-Methyl D-Aspartate (NMDA) receptors. Rats were treated once daily with an EMPA (5 and 10 mg/kg) and donepezil (2.5 mg/kg) for successive 26 days. During the final 13 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. EMPA was found to be significantly reduce escape latency, increase time spent in the target quadrant, and enhanced the number of target zone crossings in the Morris water maze (MWM) test, indicating improved spatial memory. Moreover, EMPA increased the recognition index and the number of spontaneous alternations in the novel object recognition (NOR) and Y-maze tests, respectively, suggesting enhanced memory. Additionally, doses of EMPA (5 mg/kg, 10 mg/kg) exhibited memory-enhancing effects even in the absence of scopolamine-induced impairment. Biochemical analysis revealed that EMPA elevated the levels of glutathione (GSH), a potent antioxidant, while decreasing lipid peroxidation (LPO) activity and increasing catalase (CAT) levels, indicating its antioxidative properties. Interestingly molecular docking studies revealed that EMPA fit perfectly in the active sites of M1 muscarinic acetylcholine (mACh) and NMDA receptors. These results indicated that the nootropic and antiamnesic effect of EMPA is medicated via M1 and NMDA receptors and might be a pertinent solution for the AD.},
}

@article {pmid38625863,
year = {2024},
author = {Lee, C and Friedman, A},
title = {Generating PET scan patterns in Alzheimer's by a mathematical model.},
journal = {PloS one},
volume = {19},
number = {4},
pages = {e0299637},
pmid = {38625863},
issn = {1932-6203},
mesh = {Humans ; *Alzheimer Disease/pathology ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; Positron-Emission Tomography ; Models, Theoretical ; },
abstract = {Alzheimer disease (AD) is the most common form of dementia. The cause of the disease is unknown, and it has no cure. Symptoms include cognitive decline, memory loss, and impairment of daily functioning. The pathological hallmarks of the disease are aggregation of plaques of amyloid-β (Aβ) and neurofibrillary tangles of tau proteins (τ), which can be detected in PET scans of the brain. The disease can remain asymptomatic for decades, while the densities of Aβ and τ continue to grow. Inflammation is considered an early event that drives the disease. In this paper, we develop a mathematical model that can produce simulated patterns of (Aβ,τ) seen in PET scans of AD patients. The model is based on the assumption that early inflammations, R and [Formula: see text], drive the growth of Aβ and τ, respectively. Recently approved drugs can slow the progression of AD in patients, provided treatment begins early, before significant damage to the brain has occurred. In line with current longitudinal studies, we used the model to demonstrate how to assess the efficacy of such drugs when given years before the disease becomes symptomatic.},
}

Humans
*Alzheimer Disease/pathology
tau Proteins/metabolism
Amyloid beta-Peptides/metabolism
Positron-Emission Tomography
Models, Theoretical

@article {pmid38625441,
year = {2024},
author = {Besin, V and Humardani, FM and Yulianti, T and Putra, SED and Triana, R and Justyn, M},
title = {The Apo gene's genetic variants: hidden role in Asian vascular risk.},
journal = {Neurogenetics},
volume = {},
number = {},
pages = {},
pmid = {38625441},
issn = {1364-6753},
abstract = {Vascular risk factors, including diabetes, hypertension, hyperlipidemia, and obesity, pose significant health threats with implications extending to neuropsychiatric disorders such as stroke and Alzheimer's disease. The Asian population, in particular, appears to be disproportionately affected due to unique genetic predispositions, as well as epigenetic factors such as dietary patterns and lifestyle habits. Existing management strategies often fall short of addressing these specific needs, leading to greater challenges in prevention and treatment. This review highlights a significant gap in our understanding of the impact of genetic screening in the early detection and tailored treatment of vascular risk factors among the Asian population. Apolipoprotein, a key player in cholesterol metabolism, is primarily associated with dyslipidemia, yet emerging evidence suggests its involvement in conditions such as diabetes, hypertension, and obesity. While genetic variants of vascular risk are ethnic-dependent, current evidence indicates that epigenetics also exhibits ethnic specificity. Understanding the interplay between Apolipoprotein and genetics, particularly within diverse ethnic backgrounds, has the potential to refine risk stratification and enhance precision in management. For Caucasian carrying the APOA5 rs662799 C variant, pharmacological interventions are recommended, as dietary interventions may not be sufficient. In contrast, for Asian populations with the same genetic variant, dietary modifications are initially advised. Should dyslipidemia persist, the consideration of pharmaceutical agents such as statins is recommended.},
}

@article {pmid38625027,
year = {2024},
author = {Zhou, AL and Swaminathan, SK and Salian, VS and Wang, L and Curran, GL and Min, HK and Lowe, VJ and Kandimalla, KK},
title = {Insulin Signaling Differentially Regulates the Trafficking of Insulin and Amyloid Beta Peptides at the Blood-Brain Barrier.},
journal = {Molecular pharmaceutics},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.molpharmaceut.3c00784},
pmid = {38625027},
issn = {1543-8392},
abstract = {The blood-brain barrier (BBB) is instrumental in clearing toxic metabolites from the brain, such as amyloid-β (Aβ) peptides, and in delivering essential nutrients to the brain, like insulin. In Alzheimer's disease (AD) brain, increased Aβ levels are paralleled by decreased insulin levels, which are accompanied by insulin signaling deficits at the BBB. Thus, we investigated the impact of insulin-like growth factor and insulin receptor (IGF1R and IR) signaling on Aβ and insulin trafficking at the BBB. Following intravenous infusion of an IGF1R/IR kinase inhibitor (AG1024) in wild-type mice, the BBB trafficking of [125]I radiolabeled Aβ peptides and insulin was assessed by dynamic SPECT/CT imaging. The brain efflux of [[125]I]iodo-Aβ42 decreased upon AG1024 treatment. Additionally, the brain influx of [[125]I]iodoinsulin, [[125]I]iodo-Aβ42, [[125]I]iodo-Aβ40, and [[125]I]iodo-BSA (BBB integrity marker) was decreased, increased, unchanged, and unchanged, respectively, upon AG1024 treatment. Subsequent mechanistic studies were performed using an in vitro BBB cell model. The cell uptake of [[125]I]iodoinsulin, [[125]I]iodo-Aβ42, and [[125]I]iodo-Aβ40 was decreased, increased, and unchanged, respectively, upon AG1024 treatment. Further, AG1024 reduced the phosphorylation of insulin signaling kinases (Akt and Erk) and the membrane expression of Aβ and insulin trafficking receptors (LRP-1 and IR-β). These findings reveal that insulin signaling differentially regulates the BBB trafficking of Aβ peptides and insulin. Moreover, deficits in IGF1R and IR signaling, as observed in the brains of type II diabetes and AD patients, are expected to increase Aβ accumulation while decreasing insulin delivery to the brain, which has been linked to the progression of cognitive decline in AD.},
}

@article {pmid38623983,
year = {2024},
author = {Sen, D and Rathee, S and Pandey, V and Jain, SK and Patil, UK},
title = {Comprehensive Insights into Pathophysiology of Alzheimer's Disease: Herbal Approaches for Mitigating Neurodegeneration.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050309057240404075003},
pmid = {38623983},
issn = {1875-5828},
abstract = {Alzheimer's disease [AD] is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review explores the multifaceted pathophysiology of AD, focusing on key hypotheses such as the cholinergic hypothesis, hyperphosphorylated Tau Protein and Amyloid β hypothesis, oxidative stress hypothesis, and the metal ion hypothesis. Understanding these mechanisms is crucial for developing effective therapeutic strategies. Current treatment options for AD have limitations, prompting the exploration of alternative approaches, including herbal interventions. Cholinesterase inhibitors, targeting the cholinergic hypothesis, have shown modest efficacy in managing symptoms. Blocking Amyloid β [Aβ] and targeting hyperphosphorylated tau protein are under investigation, with limited success in clinical trials. Oxidative stress, implicated in AD pathology, has led to the investigation of antioxidants. Natural products, such as Punica granatum Linn, Radix Scutellariae, and Curcuma longa have demonstrated antioxidant properties, along with anti-inflammatory effects, offering potential neuroprotective benefits. Several herbal extracts, including Ginkgo biloba, Bacopa monnieri, and Withania somnifera, have shown promise in preclinical studies. Compounds like Huperzine A, Melatonin, and Bryostatin exhibit neuroprotective effects through various mechanisms, including cholinergic modulation and anti-inflammatory properties. However, the use of herbal drugs for AD management faces limitations, including standardization issues, variable bioavailability, and potential interactions with conventional medications. Additionally, the efficacy and safety of many herbal products remain to be established through rigorous clinical trials. This review also highlights promising natural products currently in clinical trials, such as Resveratrol and Homotaurine, and their potential impact on AD progression. DHA, an omega-3 fatty acid, has shown cognitive benefits, while Nicotine is being explored for its neuroprotective effects. In conclusion, a comprehensive understanding of the complex pathophysiology of AD and the exploration of herbal interventions offer a holistic approach to managing this devastating disease. Future research should address the limitations associated with herbal drugs and further evaluate the efficacy of promising natural products in clinical settings.},
}

@article {pmid38623856,
year = {2024},
author = {Kovalová, M and Gottfriedová, N and Mrázková, E and Janout, V and Janoutová, J},
title = {Cognitive impairment, neurodegenerative disorders, and olfactory impairment: A literature review.},
journal = {Otolaryngologia polska = The Polish otolaryngology},
volume = {78},
number = {2},
pages = {1-17},
doi = {10.5604/01.3001.0053.6158},
pmid = {38623856},
issn = {2300-8423},
mesh = {Humans ; *Cognitive Dysfunction/complications/diagnosis/psychology ; *Alzheimer Disease/complications/diagnosis/psychology ; *Olfaction Disorders/diagnosis/etiology ; Smell ; },
abstract = {
Introduction: The early detection and diagnosis of dementia are of key importance in treatment, slowing disease progression, or suppressing symptoms. The possible role of changes in the sense of smell is considered with regard to potential markers for early detection of Alzheimer's disease (AD).

Materials and methods: A literature search was conducted using the electronic databases PubMed, Scopus, and Web of Science between May 30, 2022 and August 2, 2022. The term "dementia" was searched with keyword combinations related to olfaction.

Results: A total of 1,288 records were identified through the database search. Of these articles, 49 were ultimately included in the analysis. The results showed the potential role of changes in the sense of smell as potential biomarkers for early detection of AD. Multiple studies have shown that olfactory impairment may be observed in patients with AD, PD, MCI, or other types of dementia. Even though smell tests are able to detect olfactory loss caused by neurodegenerative diseases, they cannot reliably distinguish between certain diseases.

Conclusions: In individuals with cognitive impairment or neurodegenerative diseases, olfactory assessment has repeatedly been reported to be used for early diagnosis, but not for differential diagnosis. }

Humans
*Cognitive Dysfunction/complications/diagnosis/psychology
*Alzheimer Disease/complications/diagnosis/psychology
*Olfaction Disorders/diagnosis/etiology
Smell

@article {pmid38623574,
year = {2024},
author = {Li, L and Huang, Z and Wu, M and Li, X and Xiao, B and Yao, D and Mo, B},
title = {Trehalose improves the movement ability of AβarcDrosophila by restoring the damaged mitochondria.},
journal = {Translational neuroscience},
volume = {15},
number = {1},
pages = {20220338},
doi = {10.1515/tnsci-2022-0338},
pmid = {38623574},
issn = {2081-3856},
abstract = {BACKGROUND: The deposition of Aβ42 has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aβ42 toxicity has been progressed slowly.

OBJECTIVE: Our aim was to introduce the effect and related mechanism of trehalose on an Aβarc (arctic mutant Aβ42) Drosophila AD model.

METHODS: The human Aβarc was expressed in Drosophila to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aβarc, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function.

RESULTS: Trehalose strongly improved the movement ability of Aβarc Drosophila in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aβarc and lactate both in the brain and thorax of Aβarc Drosophila. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in Aβarc Drosophila.

CONCLUSION: Trehalose improves movement ability at least partly by reducing the Aβarc level and restoring the mitochondrial structure and function in Aβarc Drosophila.},
}

@article {pmid38623385,
year = {2024},
author = {Crump, C and Sieh, W and Vickrey, BG and Edwards, AC and Sundquist, J and Sundquist, K},
title = {Risk of depression in persons with Alzheimer's disease: A national cohort study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {16},
number = {2},
pages = {e12584},
pmid = {38623385},
issn = {2352-8729},
support = {R03 AG083596/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD.

METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998-2017 in Sweden, and 3,900,880 age- and sex-matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018.

RESULTS: Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two-fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11-2.32) or men with AD (2.68; 2.52-2.85), compared with controls. Similar results were found for all-cause dementia.

DISCUSSION: Persons diagnosed with AD or related dementias need close follow-up for timely detection and treatment of depression.

HIGHLIGHTS: In a large cohort, women and men with AD had >2-fold subsequent risk of depression.Risks were highest in the first year (>3-fold) but remained elevated ≥3 years later.Risk of depression was highest in persons aged ≥85 years at AD diagnosis.Persons with AD need close follow-up for detection and treatment of depression.},
}

@article {pmid38623384,
year = {2024},
author = {Schworer, EK and Handen, BL and Petersen, M and O'Bryant, S and Peven, JC and Tudorascu, DL and Lee, L and Krinsky-McHale, SJ and Hom, CL and Clare, ICH and Christian, BT and Schupf, N and Lee, JH and Head, E and Mapstone, M and Lott, I and Ances, BM and Zaman, S and Brickman, AM and Lai, F and Rosas, HD and Hartley, SL and , },
title = {Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {16},
number = {2},
pages = {e12582},
pmid = {38623384},
issn = {2352-8729},
abstract = {INTRODUCTION: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.

METHODS: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years).

RESULTS: In general linear models lower plasma Aβ42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory.

DISCUSSION: Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest.

HIGHLIGHTS: Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome.Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities.Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance.Plasma biomarkers show potential for tracking early stages of AD symptomology.},
}

@article {pmid38623383,
year = {2024},
author = {Sukreet, S and Rafii, MS and Rissman, RA},
title = {From understanding to action: Exploring molecular connections of Down syndrome to Alzheimer's disease for targeted therapeutic approach.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {16},
number = {2},
pages = {e12580},
pmid = {38623383},
issn = {2352-8729},
abstract = {Down syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid-beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD. As a result, people with DS are a key demographic for research into AD therapeutics and prevention. The molecular links between DS and AD shed insights into the underlying causes of both diseases and highlight potential therapeutic targets. Also, using biomarkers for early diagnosis and treatment monitoring is an active area of research, and genetic screening for high-risk individuals may enable earlier intervention. Finally, the fundamental mechanistic parallels between DS and AD emphasize the necessity for continued research into effective treatments and prevention measures for DS patients at risk for AD. Genetic screening with customized therapy approaches may help the DS population in current clinical studies and future biomarkers.},
}

@article {pmid38623278,
year = {2024},
author = {Inci, OK and Basırlı, H and Can, M and Yanbul, S and Seyrantepe, V},
title = {Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.},
journal = {Journal of lipids},
volume = {2024},
number = {},
pages = {4530255},
pmid = {38623278},
issn = {2090-3030},
abstract = {Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.},
}

@article {pmid38623052,
year = {2024},
author = {Guzmán-Ocampo, DC and Aguayo-Ortiz, R and Dominguez, L},
title = {Understanding the Modulatory Role of E2012 on the γ-Secretase-Substrate Interaction.},
journal = {Journal of chemical information and modeling},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jcim.3c01993},
pmid = {38623052},
issn = {1549-960X},
abstract = {Allosteric modulation plays a critical role in enzyme functionality and requires a deep understanding of the interactions between the active and allosteric sites. γ-Secretase (GS) is a key therapeutic target in the treatment of Alzheimer's disease (AD), through its role in the synthesis of amyloid β peptides that accumulate in AD patients. This study explores the structure and dynamic effects of GS modulation by E2012 binding, employing well-tempered metadynamics and conventional molecular dynamics simulations across three binding scenarios: (1) GS enzyme with and without L458 inhibitor, (2) the GS-substrate complex together with the modulator E2012 in two different binding modes, and (3) E2012 interacting with a C99 substrate fragment. Our findings reveal that the presence of L458 induces conformational changes that contribute to stabilization of the GS enzyme dynamics, previously reported as a key factor that allowed the resolution of the cryo-EM structure and the enhanced binding of E2012. Furthermore, we identified the most favorable binding site for E2012 within the GS-substrate complex, uncovering significant modulatory effects and a complex network of interactions that influence the position of the substrate for catalysis. In addition, we explore a potential substrate-modulator binding before the formation of the enzyme-substrate complex. The insights gained from our study emphasize the importance of these interactions in the development of potential therapeutic interventions that target the functionality of the GS enzyme in AD.},
}

@article {pmid38621897,
year = {2024},
author = {Wang, CH and Wei, XT and Zhao, YQ and Wang, DH and Xue, JJ and Song, ZQ and Tang, F and Liu, RX and Wang, CA},
title = {[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].},
journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica},
volume = {49},
number = {4},
pages = {902-911},
doi = {10.19540/j.cnki.cjcmm.20230913.403},
pmid = {38621897},
issn = {1001-5302},
mesh = {Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Amyloid beta-Peptides/metabolism ; Medicine, Chinese Traditional ; Quality of Life ; *Alzheimer Disease/drug therapy/prevention & control ; *Cognitive Dysfunction/drug therapy/prevention & control ; },
abstract = {Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid β-protein(Aβ) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aβ deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.},
}

Humans
Inflammasomes/metabolism
NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
Amyloid beta-Peptides/metabolism
Medicine, Chinese Traditional
Quality of Life
*Alzheimer Disease/drug therapy/prevention & control
*Cognitive Dysfunction/drug therapy/prevention & control

@article {pmid38621736,
year = {2024},
author = {Cheng, L and Zhu, C and Zhou, B and Zhang, J and Wang, C and Song, R and Tao, L},
title = {Visual analysis on the study status and trends of acupuncture and moxibustion for Alzheimer's disease.},
journal = {Zhongguo zhen jiu = Chinese acupuncture & moxibustion},
volume = {44},
number = {4},
pages = {469-478},
doi = {10.13703/j.0255-2930.20230721-k0003},
pmid = {38621736},
issn = {0255-2930},
mesh = {Animals ; Mice ; *Moxibustion ; *Alzheimer Disease/therapy ; *Acupuncture Therapy ; *Electroacupuncture ; Acupuncture Points ; },
abstract = {The research history, hot spots and frontier trends of acupuncture and moxibustion for Alzheimer's disease (AD) were explored using knowledge graph technology. The articles on acupuncture and moxibustion for AD were searched from 6 databases, i.e. CNKI, VIP, Wanfang, SinoMed, Pubmed and Web of Science, from January 1st, 1993 to January 1st, 2023. Using CiteSpace6.2.R2 Advance and VOSviewer V1.6.19 softwares, the knowledge map was graphed and the visual analysis was performed. A total of 1 228 Chinese and 309 English articles were included. The high-frequency keywords were generally divided into the keywords of clinical diseases (AD, dementia), those of therapeutic methods (electroacupuncture, acupuncture-moxibustion and acupuncture) and those of mechanism study (β-amyloid, mice). Thirteen keyword clusters were formed among the articles of Chinese version, e.g. acupuncture-moxibustion, dementia, acupuncture and electroacupuncture; and 8 clusters were obtained among English articles, e.g. electroacupuncture, drug therapy and hippocampus. The high-frequency keywords of acupoints included Baihui (GV 20), Dazhui (GV 14), Yintang (GV 24[+]), Zusanli (ST 36), Fenglong (ST 40), etc. Six clusters of "acupuncture techniques → acupoints" were obtained for the treatment of AD with acupuncture and moxibustion. The therapeutic methods and modes of AD with acupuncture and moxibustion are constantly progressed, the development of clinical research tends to the evaluation of novel therapeutic mode and clinical effect, and the mechanism of acupuncture and moxibustion for the effect on AD are more deeply explored. Among the various therapeutic methods, acupuncture-moxibustion, acupuncture and electroacupuncture have been early predominant; while, many novel methods are gradually displayed later, such as music electroacupuncture and hydro-acupuncture. In recent 30 years, among Chinese and English articles for the studies of AD treated with acupuncture and moxibustion, the theme of them focuses on the two aspects, the observation of clinical effect and the mechanism research. It is found that the clinical therapeutic methods have been gradually improved and the mechanism exploration been deepened.},
}

Animals
Mice
*Moxibustion
*Alzheimer Disease/therapy
*Acupuncture Therapy
*Electroacupuncture
Acupuncture Points