Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia

Neurology, Journal Year: 2024, Volume and Issue: 102(4)

Published: Jan. 30, 2024

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored utility plasma as for accelerated aging and dementia risk.

Language: Английский

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A critical appraisal of tau‐targeting therapies for primary and secondary tauopathies

Alzheimer s & Dementia, Journal Year: 2021, Volume and Issue: 18(5), P. 1008 - 1037

Published: Sept. 17, 2021

Abstract Introduction Primary tauopathies are neurological disorders in which tau protein deposition is the predominant pathological feature. Alzheimer's disease a secondary tauopathy with forming hyperphosphorylated insoluble aggregates. Tau pathology can propagate from region to brain, while alterations processing may impair physiological functions. Methods We reviewed literature on biology and anti‐tau drugs using PubMed, meeting abstracts, ClnicalTrials.gov. Results The past 15 years have seen >30 interfering aggregation, processing, accumulation reaching clinic. Initial results aggregation inhibitors monoclonal antibodies not shown clinical efficacy. Discussion reasons for these failures unclear but could be linked clearing of forms by non‐specific drugs. Research now concentrating efforts developing reliable translational animal models selective compounds targeting specific epitopes, neurotoxic aggregates, post‐translational modifications.

Language: Английский

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The clock modulator Nobiletin mitigates astrogliosis‐associated neuroinflammation and disease hallmarks in an Alzheimer’s disease model

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(3)

Published: Feb. 4, 2022

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, and there pressing need to identify disease-modifying factors devise interventional strategies. The circadian clock, our intrinsic biological timer, orchestrates various cellular physiological processes including gene expression, sleep, neuroinflammation; conversely, dysfunctions are closely associated with and/or contribute AD hallmarks. We previously reported that the natural compound Nobiletin (NOB) clock-enhancing modulator promotes health healthy aging. In current study, we treated double transgenic model mice, APP/PS1, NOB-containing diets. NOB significantly alleviated β-amyloid burden in both hippocampus cortex, exhibited trend improve cognitive function these mice. While several systemic parameters for wheel-running activity, metabolism were unchanged, treatment showed marked effect on expression of clock clock-controlled cortex. accordance, cortical proteomic profiling demonstrated time-dependent restoration protein landscape APP/PS1 mice NOB. More importantly, found potent efficacy inhibit proinflammatory cytokine inflammasome formation immunostaining further revealed specific diminish astrogliosis, but not microgliosis, by Together, results underscore beneficial effects mitigate pathological hallmarks AD, suggest possible mechanism via suppressing astrogliosis-associated neuroinflammation.

Language: Английский

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Astrocytes deficient in circadian clock gene Bmal1 show enhanced activation responses to amyloid-beta pathology without changing plaque burden

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Feb. 2, 2022

Abstract An emerging link between circadian clock function and neurodegeneration has indicated a critical role for the molecular in brain health. We previously reported that deletion of core gene Bmal1 abrogates induces cell-autonomous astrocyte activation. Regulation activation important implications protein aggregation, inflammation, neuronal survival neurodegenerative conditions such as Alzheimer's disease (AD). Here, we investigated how induced by regulates expression, amyloid-beta (Aβ) plaque-associated activation, plaque deposition. To address these questions, crossed astrocyte-specific knockout mice (Aldh1l1-Cre ERT2 ;Bmal1 fl/fl , termed BMAL1 aKO), to APP/PS1-21 APP NL-G-F models Aβ accumulation. Transcriptomic profiling showed aKO unique transcriptional profile affecting genes involved both generation elimination Aβ. exacerbated around plaques altered expression. However, this astrogliosis did not affect accumulation or dystrophy either model. Our results demonstrate striking does influence deposition, which indicates effect on pathology general is highly dependent mechanism

Language: Английский

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Microglia in Alzheimer's Disease: a Key Player in the Transition Between Homeostasis and Pathogenesis

Neurotherapeutics, Journal Year: 2022, Volume and Issue: 19(1), P. 186 - 208

Published: Jan. 1, 2022

Language: Английский

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