Research models to study lewy body dementia DOI Creative Commons
Suelen L. Boschen,

Aarushi A. Mukerjee,

Ayman H. Faroqi

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 23, 2025

Abstract Lewy body dementia (LBD) encompasses neurodegenerative dementias characterized by cognitive fluctuations, visual hallucinations, and parkinsonism. Clinical differentiation of LBD from Alzheimer’s disease (AD) remains complex due to symptom overlap, yet approximately 25% cases are diagnosed as postmortem, primarily identified the presence α-synuclein aggregates, tau tangles, amyloid plaques. These pathological features position a comorbid condition both Parkinson’s (PD) AD, with over 50% exhibiting co-pathologies. LBD’s mixed pathology complicates development comprehensive models that reflect full spectrum etiological, clinical, features. While existing animal cellular have facilitated significant discoveries in PD AD research, they lack specificity capturing unique pathogenic mechanisms, limiting exploration therapeutic avenues for specifically. This review assesses widely used terms their relevance LBD, particularly focusing on ability replicate human assess treatment efficacy. Furthermore, we discuss potential modifications these advance understanding mechanisms propose innovative research directions aimed at developing enhanced face, predictive, construct validity.

Language: Английский

Multi-omics analysis of druggable genes to facilitate Alzheimer's disease therapy: A multi-cohort machine learning study DOI Creative Commons
Jichang Hu,

Yong Luo,

Xiaochuan Wang

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100128 - 100128

Published: March 1, 2025

The swift rise in the prevalence of Alzheimer's disease (AD) alongside its significant societal and economic impact has created a pressing demand for effective interventions treatments. However, there are no available treatments that can modify progression disease. Eight AD brain tissues datasets three blood were obtained. Consensus clustering was utilized as method to discern various subtypes AD. Then, module genes screened using weighted correlation network analysis (WGCNA). Furthermore, screening hub conducted through machine-learning analyses. Finally, A comprehensive systematic approach druggable genome-wide Mendelian randomization (MR) conducted. Two subclasses identified, namely cluster.A cluster.B. levels gamma secretase activity, beta amyloid-beta 42 found be significantly elevated patients classified within cluster when compared those B. by utilizing differentially expressed shared among these clusters, along with identifying applying WGCNA subtypes, we able develop scoring system referred DG.score. This demonstrated remarkable predictive capability evaluated against multiple datasets. Besides, total 30 distinct may serve potential drug targets identified across at least one investigated, whether derived from samples or Among genes, specific candidates considered (LIMK2, MAPK8, NDUFV2) expression both tissues. our research also revealed association between LIMK2 concentrations CSF Aβ (OR 1.526 (1.155-2.018)), p-tau 1.106 (1.024-01.196)), hippocampal size 0.831 (0.702-0.948)). study provides notable advancement existing literature offering genetic evidence underscores therapeutic advantages focusing on gene treatment insight not only contributes understanding but guides future discovery efforts.

Language: Английский

Citations

0
Sequential Proteomic Analysis Reveals the Key APOE4‐Induced Pathological and Molecular Features at the Presymptomatic Stage in Alzheimer's Disease Mice DOI Creative Commons

Pengju Wei,

Kaihua Lin,

Xuhui Chen

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: March 1, 2025

Alzheimer's disease (AD) involves a prolonged presymptomatic or preclinical stage with subtle pathological changes. Apolipoprotein E4 (APOE4) is significant genetic risk factor for AD, yet its specific role at the not fully understood. This study aimed to elucidate cellular and molecular effects of APOE4 compared APOE3 on AD progression during stage. We generated 5xFAD mice carrying human their non-AD controls. Behavioral tests, immunostaining, quantitative proteomics phosphoproteomics, Golgi staining, Western blotting were conducted 3 10 months age, respectively. Cell culture experiments performed assess APOE4's direct impact neuronal mitochondrial function. significantly increased β-amyloid (Aβ) deposition microglial activation in stage, without aggravating blood-brain barrier disruption. Proteomic biochemical analysis revealed strong features synaptic degeneration dysfunction associated APOE4. Notably, promoted fusion mitophagy while inhibiting fission, leading impaired energy supply reactive oxygen species. Our findings indicate that accelerates pathologies by exacerbating Aβ deposition, neuroinflammation, degeneration. The highlights as critical mediator APOE4-induced progression, providing potential targets early intervention.

Language: Английский

Citations

0
Cognitive Frailty: A Comprehensive Clinical Paradigm Beyond Cognitive Decline DOI
Mariagiovanna Cozza, Virginia Boccardi

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102738 - 102738

Published: March 1, 2025

Language: Английский

Citations

0
Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View DOI Creative Commons

Antonella Di Sarno,

Fiammetta Romano,

R Arianna

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(4), P. 282 - 282

Published: April 18, 2025

Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role lipid metabolism in health central nervous system. The aim our work was to provide an update on this topic, with focus clinical practice from endocrinological point view. Endocrinologists, being experts management dyslipidemias, can play key prevention treatment conditions, through precocious effective profile optimization. Methods: literature scanned identify trials correlation studies association dyslipidemia, statin therapy, following diseases: Alzheimer’s disease (AD), Parkisons’s (PD), Multiple sclerosis (MS), Amyotrophic lateral (ALS). Results: Impaired homeostasis, such as that frequently observed patients affected by obesity diabetes, is related AD, PD, other cognitive deficits aging. AD dementias are now real priority problem. In United States, there approximately 7 million subjects aged 65 older living dementias, number projected grow 12 coming decades. Lipid-lowering therapy statins strategy reducing serum low-density lipoprotein cholesterol normal range concentrations and, therefore, cardiovascular risk; moreover, have been reported positive effect diseases. Conclusions: Several pieces research found inconsistent information review. There no use ALS incidence. More has emerged regarding AD/PD. However, further large-scale prospective randomized control required properly understand issue.

Language: Английский

Citations

0
Research models to study lewy body dementia DOI Creative Commons
Suelen L. Boschen,

Aarushi A. Mukerjee,

Ayman H. Faroqi

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 23, 2025

Abstract Lewy body dementia (LBD) encompasses neurodegenerative dementias characterized by cognitive fluctuations, visual hallucinations, and parkinsonism. Clinical differentiation of LBD from Alzheimer’s disease (AD) remains complex due to symptom overlap, yet approximately 25% cases are diagnosed as postmortem, primarily identified the presence α-synuclein aggregates, tau tangles, amyloid plaques. These pathological features position a comorbid condition both Parkinson’s (PD) AD, with over 50% exhibiting co-pathologies. LBD’s mixed pathology complicates development comprehensive models that reflect full spectrum etiological, clinical, features. While existing animal cellular have facilitated significant discoveries in PD AD research, they lack specificity capturing unique pathogenic mechanisms, limiting exploration therapeutic avenues for specifically. This review assesses widely used terms their relevance LBD, particularly focusing on ability replicate human assess treatment efficacy. Furthermore, we discuss potential modifications these advance understanding mechanisms propose innovative research directions aimed at developing enhanced face, predictive, construct validity.

Language: Английский

Citations

0