CSF α-synuclein aggregation is associated with APOE ε4 and progressive cognitive decline in Alzheimer's disease

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging Pub Date : 2025-02-27 DOI:10.1016/j.neurobiolaging.2025.02.008

Qiang Qiang , Loren Skudder-Hill , Tomoko Toyota , Zhe Huang , Wenshi Wei , Hiroaki Adachi , Alzheimer’s Disease Neuroimaging Initiative

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引用次数: 0

Abstract

At autopsy, around half of the Alzheimer's disease (AD) brains exhibit Lewy body pathology, and the main component of Lewy body pathology is α-synuclein aggregates. This study investigated the prevalence of cerebrospinal fluid (CSF) α-synuclein aggregation and its association with demographic factors and cognitive decline among 1619 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with the test for α-synuclein aggregation by seed amplification assay (SAA). This cohort consisted of 595 cognitively normal (CN) individuals, 765 with mild cognitive impairment (MCI), and 259 with AD dementia. The results showed a higher prevalence of positive α-synuclein aggregation status in the AD dementia group (37.07 %) and the MCI group (22.75 %) compared to CN controls (16.13 %). Additionally, APOE ε4 carriers exhibited a higher prevalence of α-synuclein aggregation compared to non-carriers: 20.12 % for APOE ε4-/- (non-carriers), 24.82 % for APOE ε4 + /-, and 30.92 % for APOE ε4 + /+ . Longitudinally, positive CSF α-synuclein aggregation associated with accelerated cognitive decline, especially in the MCI and AD groups. Notably, positive aggregation status did not significantly affect cognitive trajectories in CN individuals. Moreover, APOE ε4 carriers with positive CSF α-synuclein aggregation experienced more pronounced cognitive decline. This study provides evidence that CSF α-synuclein aggregation is associated with cognitive function and the APOE ε4 allele. These findings suggest that CSF α-synuclein SAA, in combination with APOE ε4 status, could serve as biomarkers for predicting cognitive decline in AD.

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来源期刊

Neurobiology of Aging 医学-老年医学

CiteScore

8.40

自引率

2.40%

发文量

225

审稿时长

67 days

期刊介绍： Neurobiology of Aging publishes the results of studies in behavior, biochemistry, cell biology, endocrinology, molecular biology, morphology, neurology, neuropathology, pharmacology, physiology and protein chemistry in which the primary emphasis involves mechanisms of nervous system changes with age or diseases associated with age. Reviews and primary research articles are included, occasionally accompanied by open peer commentary. Letters to the Editor and brief communications are also acceptable. Brief reports of highly time-sensitive material are usually treated as rapid communications in which case editorial review is completed within six weeks and publication scheduled for the next available issue.