Misfolded alpha synuclein co-occurrence with Alzheimer's disease proteinopathy.

medRxiv : the preprint server for health sciences Pub Date : 2024-10-13 DOI:10.1101/2024.10.11.24315349

Erin M Jonaitis, Karen MacLeod, Jennifer Lamoureux, Beckie Jeffers, Rachel L Studer, John Middleton, Rachael E Wilson, Nathaniel A Chin, Ozioma C Okonkwo, Barbara B Bendlin, Sanjay Asthana, Cynthia M Carlsson, Catherine L Gallagher, Bruce Hermann, Sean McEvoy, Gwendlyn Kollmorgen, Henrik Zetterberg, Luis Concha-Marambio, Sterling C Johnson, Russ M Lebovitz, Rebecca E Langhough

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Abstract

Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded α -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).

Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.42 (7.78) years; education, 16.17 (2.23) years). synSAA results were compared to phosphorylated tau (T), beta amyloid (A), and clinical outcomes. Longitudinal cognition was modeled with mixed effects.

Results: Syn positivity (synSAA+) co-occurred with T (in synSAA+ vs synSAA-, 36% vs 20% T+; p=0.011) and with cognitive impairment (10% vs 7% MCI; 10% vs 0% dementia; p=0.00050). synSAA+ participants' cognitive performance declined ∼40% faster than synSAA-for Digit Symbol, but not other tests.

Discussion: Findings support prevalent syn copathology in a mostly-unimpaired AD risk cohort. Future work will explore relationships with disease progression.

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错误折叠的α-突触核蛋白与阿尔茨海默病蛋白病同时存在。

导言：多病因痴呆症需要体内共同病理标记物，包括折叠错误的α-突触核蛋白（syn）。我们通过定性种子扩增试验（synSAA）测量了折叠错误的突触核蛋白聚集体（syn-seeds），并研究了其与阿尔茨海默病（AD）标志物的关系：脑脊液（CSF）取自威斯康星州两个AD风险队列中的420名参与者（35%为男性；91%认知能力无障碍；平均（SD）年龄为65.42（7.78）岁；受教育程度为16.17（2.23）年）。采用混合效应建立了纵向认知模型：Syn阳性（synSAA+）与T（synSAA+ vs synSAA-，36% vs 20% T+；p=0.011）和认知障碍（10% vs 7% MCI；10% vs 0%痴呆；p=0.00050）同时存在。SynSAA+参与者的认知能力下降速度比synSAA-数字符号（Digit Symbol）快40%，但与其他测试无关：讨论：研究结果表明，在大部分未受损的AD风险队列中，普遍存在syn共病理学。未来的工作将探索与疾病进展的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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medRxiv : the preprint server for health sciences

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