Alterations in the <em>amyloid protein precursor</em>, <em>α-secretase</em>, <em>β-secretase</em>, <em>presenilins</em> and <em>tau protein</em> Genes in the CA3 Area of the Hippocampus in a 2-Year Ischemic Model of Alzheimer’s Disease DOI Open Access
Stanisław J. Czuczwar, Janusz Kocki, Barbara Miziak

et al.

Published: Sept. 30, 2023

Understanding the phenomena underlying non-selective susceptibility to ischemia of py-ramidal neurons in CA3 area hippocampus is important from point view elu-cidating mechanisms memory loss and development post-ischemic dementia. We used an ischemic model Alzheimer's disease study changes amyloid protein precursor gene expression, its cleavage enzymes tau af-ter a 10-minute brain with 12, 18, 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that expression all genes contribute pro-duction was dysregulated within 2 years after ischemia. The above control values at times study. &alpha;-secretase also exceeded throughout In contrast, &beta;-secretase reaching maximum increase 12 months ischemia, below 18 again 24 Presenilin 1 significantly elevated follow-up period, peak both occurring This suggests studied are involved non-amyloidogenic processing precursor. Also, observation present is-chemia. Data indicate episode long-term survival causes damage death pyramidal manner dependent on modified protein. Thus defining new mechanism neuronal addition modification is-chemia useful identifying disease.

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

237
The neurotransmitter puzzle of Alzheimer's: Dissecting mechanisms and exploring therapeutic horizons DOI
Monika Sharma, Pankaj Pal, Sukesh Kumar Gupta

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1829, P. 148797 - 148797

Published: Feb. 10, 2024

Language: Английский

Citations

15
Zexieyin formula alleviates Alzheimer's disease via post-synaptic CaMKII modulating AMPA receptor: Involved in promoting neurogenesis to strengthen synaptic plasticity in mice hippocampus DOI
Yan Sun, Hailou Zhang, Ruiyi Liu

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 131, P. 155802 - 155802

Published: June 4, 2024

Language: Английский

Citations

5
Identifying underlying patterns in Alzheimer's disease trajectory: a deep learning approach and Mendelian randomization analysis DOI Creative Commons
Yi Fan, Yaoyun Zhang, Jing Yuan

et al.

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 64, P. 102247 - 102247

Published: Sept. 28, 2023

Alzheimer's disease (AD) is a heterogeneously progressive neurodegeneration disorder with varied rates of deterioration, either between subjects or within different stages certain subject. Estimating the course AD at early has treatment implications. We aimed to analyze progression identify distinct patterns in trajectory.We proposed deep learning model underlying trajectory from cognitively normal (CN) state mild cognitive impairment (MCI) dementia, by jointly predicting time-to-conversion and clustering out subgroups characterized comprehensive features as well rates. designed validated our on ADNI dataset (1370 participants). Prediction was used validate expression identified patterns. Causality further inferred using Mendelian randomization (MR) analysis. External validation performed AIBL (233 participants).The clustered significantly biomarkers The discovered also showed strong prediction ability, indicated hazard ratio (CN→MCI, HR = 3.51, p < 0.001; MCI→AD, 8.11, 0.001), C-Index 0.618; 0.718), AUC 3 years 0.802, 5 0.876; 0.914, 0.957). In external cohort, demonstrated competitive performance conversion time 0.693; 0.752). Moreover, suggestive associations CN→MCI/MCI→AD four/three SNPs were mediated MR analysis causal link MCI→AD first three years.Our identifies biologically clinically meaningful real-world data provides promising trajectory, which could promote understanding progression, facilitate clinical trial design, provide potential for decision-making.The National Key Research Development Program China, R&D Zhejiang, Nature Science Foundation China.

Language: Английский

Citations

12
Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease DOI Creative Commons

Anett Futácsi,

Kitti Rusznák,

Gergely Szarka

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 12, 2025

Background Animal models of Alzheimer’s disease (AD) are essential tools for investigating pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal glial alterations in the hippocampus medial prefrontal cortex (mPFC) young TgF344-AD rats correlated these changes with cognitive decline amyloid-β plaque load. Methods We compared non-transgenic littermate aged 7–8 months age. systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, somatostatin-positive neurons), newly generated neurons hippocampus. Spatial learning memory were assessed using Barnes maze test. Results Young had a large number amyloid plaques both mPFC, together pronounced increase microglial cell numbers. Astrocytic activation was significant mPFC. Cholecystokinin-positive numbers decreased transgenic rats, but calretinin-, not altered. Adult neurogenesis affected by genotype. spatial impairments, deficit did correlate or cellular brain. hippocampus, negatively cholecystokinin-positive neuron astrocytes. Conclusion Pronounced neuropathological found mPFC including loss hippocampal interneurons. Some load, impairment.

Language: Английский

Citations

0
Brain Age Gap as a Predictive Biomarker: Linking Aging, Lifestyle, and Neuropsychiatric Health DOI
Zhengxing Huang, Ruixia Zhang,

Yi Fan

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Background The brain age gap (BAG), a neuroimaging-derived biomarker of accelerated aging, faces translational challenges due to model inaccuracies and unclear disease-mechanism linkages. We systematically evaluated BAG's clinical relevance across neuropsychiatric disorders, cognitive trajectories, mortality, lifestyle interventions. Methods Using multi-cohort data (UK Biobank [n = 38,967], Alzheimer’s Disease Neuroimaging Initiative [ADNI; n 1,402], Parkinson’s Progression Markers [PPMI; 1,182]), we developed 3D Vision Transformer (3D-ViT) for whole-brain estimation. Survival analyses, restricted cubic splines, stratified regressions assessed BAG’s associations with cognition, 16 mortality. Lifestyle modulation effects were quantified through longitudinal BAG progression. Results demonstrated robust predictive accuracy, achieving mean absolute error (MAE) 2.68 years in the UK cohort 2.99–3.20 external validation cohorts (ADNI/PPMI). Per 1-year increment was linearly associated elevated risks Alzheimer's disease (HR 1.165, 95% CI 1.086–1.249; +16.5% risk/year), mild impairment 1.040, 1.030–1.050; +4.0%), all-cause mortality 1.12, 1.09–1.15; +12%; all p < 0.001). Individuals highest quartile (Q4) faced substantially amplified risks: 2.8-fold 2.801), 6.4-fold multiple sclerosis 6.417), 1.5-fold major depressive disorder 1.466). Notably, prodromal Parkinson's exhibited paradoxical rejuvenation (mean Δ=−1.441 years, 0.001), contrasting nonsignificant incident cases 1.830, 0.154). Cognitive decline followed nonlinear critical thresholds domain-specific emerging at Q4 (BAG > 2.48 years). interventions synergistically attenuated progression advanced neurodegeneration (Q3–Q4; 0.05), particularly smoking cessation, moderated alcohol consumption, physical activity. Interpretation: robustly predicts multimorbidity, Its stage-dependent modifiability underscore utility risk stratification personalized prevention strategies.

Language: Английский

Citations

0
Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years DOI Creative Commons
Stanisław J. Czuczwar, Janusz Kocki, Barbara Miziak

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 98(1), P. 151 - 161

Published: Feb. 20, 2024

Background: Understanding the phenomena underlying non-selective susceptibility to ischemia of pyramidal neurons in CA3 is important from point view elucidating mechanisms memory loss and development dementia. Objective: The aim study was investigate changes genes expression amyloid precursor protein, its cleaving enzymes tau protein post-ischemia with survival 12–24 months. Methods: We used an ischemic model Alzheimer’s disease above using RT-PCR protocol. Results: gene control values at all times post-ischemia. α-secretase also exceeded β-secretase increased 12 24 months post-ischemia, 18 below values. Presenilin 1 2 significantly elevated Also, throughout observation period, peak present Conclusions: suggests that studied are involved non-amyloidogenic processing protein. Additionally data indicate brain long-term causes damage death area hippocampus a modified protein-dependent manner. Thus defining new mechanism neuronal In addition modification after useful identifying occurring disease.

Language: Английский

Citations

3
Structural and functional remodeling of neural networks in β-amyloid driven hippocampal hyperactivity DOI
Jinquan Li, Yanjun Liu,

Chuhui Yin

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102468 - 102468

Published: Aug. 31, 2024

Language: Английский

Citations

3
LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer’s Disease with 2-Year Survival DOI Creative Commons
Ryszard Pluta, Janusz Kocki, Jacek Bogucki

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(23), P. 2763 - 2763

Published: Dec. 4, 2023

Explaining changes at the gene level that occur during neurodegeneration in CA3 area is crucial from point of view memory impairment and development post-ischemic dementia. An ischemic model Alzheimer’s disease was used to evaluate expression genes related amyloid transport region hippocampus after 10 min brain ischemia with survival 2, 7 30 days 12, 18 24 months. The quantitative reverse transcriptase PCR assay revealed LRP1 RAGE involved dysregulated 2 months post-ischemia hippocampus. below control values. However, its day months, an episode above values, reaching a maximum increase post-ischemia. Then, it again data indicate hippocampus, causes increased for 7–30 acute phase 1 chronic stage. In other words, early stage, increases (7–30 days). Conversely, late scavenging/cleaning activity increases, reducing and/or preventing further neuronal damage or facilitating healing damaged sites. This how new phenomenon pyramidal defined. summary, modification useful study pathways molecular factors disease.

Language: Английский

Citations

8
Identification of early Alzheimer’s disease subclass and signature genes based on PANoptosis genes DOI Creative Commons
Wen-Xu Wang,

Jincheng Lu,

Ning Pan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 22, 2024

Introduction Alzheimer’s disease (AD) is one of the most prevalent forms dementia globally and remains an incurable condition that often leads to death. PANoptosis represents emerging paradigm in programmed cell death, integrating three critical processes: pyroptosis, apoptosis, necroptosis. Studies have shown necroptosis, pyroptosis play important roles AD development. Therefore, targeting genes might lead novel therapeutic targets clinically relevant approaches. This study aims identify different molecular subtypes potential drugs for treating based on PANoptosis. Methods Differentially expressed associated with were identified via Gene Expression Omnibus (GEO) dataset GSE48350, GSE5281, GSE122063. Least Absolute Shrinkage Selection Operator (LASSO) regression was employed construct a risk model linked these genes. Consensus clustering analysis conducted define We further performed gene set variation (GSVA), functional enrichment analysis, immune infiltration investigate differences between subtypes. Additionally, protein-protein interaction (PPI) network established hub genes, DGIdb database consulted compounds Single-cell RNA sequencing utilized assess expression at cellular level across Results A total 24 differentially (APANRGs) AD, leading classification two distinct subgroups. The results indicate subgroups exhibit varying progression states, early subtype primarily dysfunctional synaptic signaling. Furthermore, we from (DEGs) clusters predicted 38 candidate treatment revealed key are predominantly neuronal cells, while differential metabolic found endothelial cells astrocytes. Conclusion In summary, subtypes, including abnormality as well immune-metabolic subtype. ten SLC17A7, SNAP25, GAD1, SLC17A6, SLC32A1, PVALB, SYP, GRIN2A, SLC12A5, SYN2, marker These findings may provide valuable insights diagnosis contribute development innovative strategies.

Language: Английский

Citations

2