Multi Layered Omics Approaches Reveal Glia Specific Alterations in Alzheimer's Disease: A Systematic Review and Future Prospects DOI Creative Commons
Özkan İş, Yuhao Min, Xue Wang

et al.

Glia, Journal Year: 2024, Volume and Issue: 73(3), P. 539 - 573

Published: Dec. 9, 2024

Alzheimer's disease (AD) is the most common neurodegenerative dementia with multi-layered complexity in its molecular etiology. Multiple omics-based approaches, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and lipidomics are enabling researchers to dissect this complexity, uncover a plethora of alterations yielding insights into pathophysiology disease. These approaches reveal multi-omics essentially all cell types brain, including glia. In systematic review, we screen literature for human studies implementing any omics approach within last 10 years, discover AD-associated perturbations brain glial cells. The findings from over 200 AD-related reviewed under four different categories: microglia, oligodendrocytes, astrocytes vascular Under each category, summarize shared unique identified cells through complementary approaches. We discuss implications these development, progression ultimately treatment complex well directions future glia

Language: Английский

Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration DOI
Riya Thapa, Asif Ahmad Bhat, Moyad Shahwan

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

Citations

8
Diastolic dysfunction in Alzheimer’s disease model mice is associated with Aβ-amyloid aggregate formation and mitochondrial dysfunction DOI Creative Commons
Richa Aishwarya, Chowdhury S. Abdullah, Naznin Sultana Remex

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 19, 2024

Alzheimer's Disease (AD) is a progressive neurodegenerative disease caused by the deposition of Aβ aggregates or neurofibrillary tangles. AD patients are primarily diagnosed with concurrent development several cardiovascular dysfunctions. While few studies have indicated presence intramyocardial aggregates, none performed detailed analyses for pathomechanism cardiac dysfunction in patients. This manuscript used aged APPSWE/PS1 Tg and littermate age-matched wildtype (Wt) mice to characterize analyze associated pathophysiology. Detailed assessment functional parameters demonstrated diastolic hearts compared Wt hearts. Muscle function evaluation showed impairment (decreased exercise tolerance muscle strength) mice. Biochemical histochemical analysis revealed aggregate accumulation myocardium. also histopathological remodeling (increased collagen myocyte cross-sectional area). Additionally, altered mitochondrial dynamics, reduced antioxidant protein levels, impaired proteostasis developed decreased OXPHOS PDH complex expressions, ETC activities, respiration. Our results that defects respiration which may collectively lead myocardial pathological remodeling.

Language: Английский

Citations

4
How do neurons age? A focused review on the aging of the microtubular cytoskeleton DOI Creative Commons

Brad Richardson,

Thomas Goedert, Shmma Quraishe

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(9), P. 1899 - 1907

Published: Dec. 14, 2023

Aging is the leading risk factor for Alzheimer's disease and other neurodegenerative diseases. We now understand that a breakdown in neuronal cytoskeleton, mainly underpinned by protein modifications to destabilization of microtubules, central pathogenesis disease. This accompanied morphological defects across somatodendritic compartment, axon, synapse. However, knowledge what occurs microtubule cytoskeleton morphology neuron during physiological aging comparatively poor. Several recent studies have suggested there an age-related increase phosphorylation key stabilizing tau, modification, which known destabilize indicates potentially structures reliant on become functionally compromised normal aging. The current literature shows reductions synaptic spine density shifts conformation might explain functional deficits. microtubular actin with increasing age extremely limited. When considering regression dendrites loss dendritic length volume reported whilst reduction soma volume/size often seen. research into cytoskeletal change limited handful demonstrating mislocalizations microtubule-associated proteins just one study directly exploring integrity microtubules. In axonal diameter appearance swellings but like dendrites, investigates microtubules others reporting or mislocalization proteins. Though these are general trends reported, clear disparities between model organisms brain regions worthy further investigation. Additionally, longitudinal neuronal/cytoskeletal should also investigate whether changes contribute not vulnerability decline nervous system function behavioral output all experience. will highlight utility, if any, fortification promotion healthy potential protection against review seeks summarize currently about hope uncovering mechanisms underpinning

Language: Английский

Citations

10
Amyloid-β Pathology Is the Common Nominator Proteinopathy of the Primate Brain Aging DOI
Isidró Ferrer

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 100(s1), P. S153 - S164

Published: July 19, 2024

Senile plaques, mainly diffuse, and cerebral amyloid-β (Aβ) angiopathy are prevalent in the aging brain of non-human primates, from lemurs to Hominidae. Aβ but not hyper-phosphorylated tau (HPtau) pathology is common nominator proteinopathy primate aging. The abundance well tolerated, impact on cognitive functions usually limited particular tasks. In contrast, human characterized by early appearance HPtau pathology, forming neurofibrillary tangles, dystrophic neurites neuritic neuropil threads, preceding deposits several decades its severity progressing selected nuclei stem, entorhinal cortex, hippocampus limbic system, neocortex, other regions. Neurofibrillary tangles correlate with impairment dementia advanced cases. linked humans altered membrane protein lipid composition, particularly involving rafts. Although similar alterations unknown senescence postulated cause activated β-amyloidogenic pathway, prevailing signature

Language: Английский

Citations

3
Multi Layered Omics Approaches Reveal Glia Specific Alterations in Alzheimer's Disease: A Systematic Review and Future Prospects DOI Creative Commons
Özkan İş, Yuhao Min, Xue Wang

et al.

Glia, Journal Year: 2024, Volume and Issue: 73(3), P. 539 - 573

Published: Dec. 9, 2024

Alzheimer's disease (AD) is the most common neurodegenerative dementia with multi-layered complexity in its molecular etiology. Multiple omics-based approaches, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and lipidomics are enabling researchers to dissect this complexity, uncover a plethora of alterations yielding insights into pathophysiology disease. These approaches reveal multi-omics essentially all cell types brain, including glia. In systematic review, we screen literature for human studies implementing any omics approach within last 10 years, discover AD-associated perturbations brain glial cells. The findings from over 200 AD-related reviewed under four different categories: microglia, oligodendrocytes, astrocytes vascular Under each category, summarize shared unique identified cells through complementary approaches. We discuss implications these development, progression ultimately treatment complex well directions future glia

Language: Английский

Citations

2