Meta-analysis of published cerebrospinal fluid proteomics data identifies and validates metabolic enzyme panel as Alzheimer’s disease biomarkers

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(4), P. 101005 - 101005

Published: April 1, 2023

To develop therapies for Alzheimer's disease, we need accurate in vivo diagnostics. Multiple proteomic studies mapping biomarker candidates cerebrospinal fluid (CSF) resulted little overlap. overcome this shortcoming, apply the rarely used concept of proteomics meta-analysis to identify an effective panel. We combine ten independent datasets identification: seven from 150 patients/controls discovery, one dataset with 20 down-selection, and two 494 validation. The discovery results 21 down-selection three, be validated additional large-scale 228 diseased 266 control samples. This resulting 3-protein panel differentiates disease (AD) controls validation cohorts areas under receiver operating characteristic curve (AUROCs) 0.83 0.87, respectively. study highlights value systematically re-analyzing previously published data more stringent deposition.

Language: Английский

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Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.

DOAJ (DOAJ: Directory of Open Access Journals), Journal Year: 2022, Volume and Issue: 3

Published: Jan. 1, 2022

Alzheimer disease is one of the most challenging demons in our society due to its very high prevalence and clinical manifestations which cause deterioration cognition, intelligence, emotions - capacities that distinguish Homo sapiens from other animal species. Besides personal, social, economical costs, late stages AD are vivid experiences for family, relatives, friends, general observers progressive ruin an individual who turns into a being with lower mental physical than less evolved A human brain healthy conscience, can succeed dealing difficulties life may pose. Without these capacities, same person probably cannot. Due, part, this emotional impact, absorbing study has generated, over years, fascinating complex story theories, hypotheses, controversies, fashion swings, passionate clashes, together tremendous efforts achievements geared improve understanding pathogenesis treatment disorder. Familal rare linked altered genetic information associated three genes. Sporadic (sAD) much more common multifactorial. major point discussion been, still is, establishing differences between aging sAD. This not trivial question, as neuropathological molecular characteristics normal first appearance early sAD-related pathology easily distinguishable individuals. Another important confidence assigning responsibility beginning sAD few triggering molecules, without considering wide number alterations converge Genetic risk factors covering multiple signals increasing number. In line, pathways at pathology, currently grouped under aegis aging, only increase massively advanced process. here considered inherent, natural part prevalent all humans, variably present or individuals The progression process devastating effects relatively low percentage beings eventually evolving dementia. continuum implies search different approach biological process, advances use new technologies aimed slowing down defects underlying outset, transfering tasks AI coordinated devices.

Language: Английский

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Voluntary exercise preserves visual function and reduces inflammatory response in an adult mouse model of autosomal dominant retinitis pigmentosa

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

Published: March 23, 2024

Abstract Whole-body physical exercise has been shown to promote retinal structure and function preservation in animal models of degeneration. It is currently unknown how modulates inflammatory responses. In this study, we investigated cytokine alterations associated with neuroprotection induced by voluntary running wheel a degeneration mouse model class B1 autosomal dominant retinitis pigmentosa, I307N Rho . mice undergo rod photoreceptor when exposed bright light (induced). Our data show, active exhibited significant visual compared inactive after 4 weeks exercise. Retinal expression revealed reductions proinflammatory chemokines, keratinocyte-derived chemokine (KC) interferon gamma inducible protein-10 (IP-10) groups groups. Through immunofluorescence, found KC IP-10 labeling localized vasculature marker, collagen IV. These show that whole-body lowers specific vasculature. Future studies should determine whether suppression responses requisite for exercise-induced protection.

Language: Английский

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Astrocyte–Neuron Interactions in Alzheimer’s Disease

Advances in neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 345 - 382

Published: Jan. 1, 2024

Language: Английский

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Tyrosine phosphorylation and palmitoylation of TRPV2 ion channel tune microglial beta-amyloid peptide phagocytosis

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Sept. 3, 2024

Alzheimer's disease (AD) is the leading form of dementia, characterized by accumulation and aggregation amyloid in brain. Transient receptor potential vanilloid 2 (TRPV2) an ion channel involved diverse physiopathological processes, including microglial phagocytosis. Previous studies suggested that cannabidiol (CBD), activator TRPV2, improves amyloid-β (Aβ) phagocytosis TRPV2 modulation. However, molecular mechanism Aβ remains unknown. In this study, we aimed to investigate involvement underlying mechanisms. Utilizing human datasets, mouse primary neuron microglia cultures, AD model mice, evaluate expression both vivo vitro. was expressed cortex, hippocampus, microglia.Cannabidiol (CBD) could activate sensitize channel. Short-term CBD (1 week) injection intraperitoneally (i.p.) reduced neuroinflammation phagocytic receptors, but long-term (3 administration induced suppressed receptors APP/PS1 mice. Furthermore, hyper-sensitivity mediated tyrosine phosphorylation at sites Tyr(338), Tyr(466), Tyr(520) protein kinase JAK1, these mutation partially dependence on its localization. While palmitoylated Cys 277 site blocking palmitoylation improved Moreover, it demonstrated dynamically regulated ZDHHC21. Overall, our findings elucidated intricate interplay between phosphorylation/dephosphorylation cysteine palmitoylation/depalmitoylation, which had divergent effects These provide valuable insights into mechanisms linking sensitivity, offer therapeutic strategies for managing AD.

Language: Английский

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