额颞叶变性
神经颗粒素
神经科学
路易体
病理
脑脊液
生物标志物
神经退行性变
阿尔茨海默病
失智症
医学
疾病
生物
痴呆
生物化学
蛋白激酶C
酶
作者
Johanna Nilsson,Katheryn A.Q. Cousins,Johan Gobom,Erik Portelius,Alice Chen‐Plotkin,Leslie M. Shaw,Murray Grossman,David J. Irwin,John Q. Trojanowski,Henrik Zetterberg,Kaj Blennow,Ann Brinkmalm
摘要
Synaptic degeneration is a key part of the pathophysiology of neurodegenerative diseases, and biomarkers reflecting the pathological alterations are greatly needed.Seventeen synaptic proteins were quantified in a pathology-confirmed cerebrospinal fluid cohort of patients with Alzheimer's disease (AD; n = 63), frontotemporal lobar degeneration (FTLD; n = 53), and Lewy body spectrum of disorders (LBD; n = 21), as well as healthy controls (HC; n = 48).Comparisons revealed four distinct patterns: markers decreased across all neurodegenerative conditions compared to HC (the neuronal pentraxins), markers increased across all neurodegenerative conditions (14-3-3 zeta/delta), markers selectively increased in AD compared to other neurodegenerative conditions (neurogranin and beta-synuclein), and markers selectively decreased in LBD and FTLD compared to HC and AD (AP2B1 and syntaxin-1B).Several of the synaptic proteins may serve as biomarkers for synaptic dysfunction in AD, LBD, and FTLD. Additionally, differential patterns of synaptic protein alterations seem to be present across neurodegenerative diseases.A panel of synaptic proteins were quantified in the cerebrospinal fluid using mass spectrometry. We compared Alzheimer's disease, frontotemporal degeneration, and Lewy body spectrum of disorders. Pathology was confirmed by autopsy or familial mutations. We discovered synaptic biomarkers for synaptic degeneration and cognitive decline. We found differential patterns of synaptic proteins across neurodegenerative diseases.
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