Association of naturally occurring antibodies to β-amyloid with cognitive decline and cerebral amyloidosis in Alzheimer’s disease

Yu Hui Liu, Jun Wang, Qiao Xin Li, Christopher J. Fowler, Fan Zeng, Juan Deng, Zhi Qiang Xu, Hua Dong Zhou, James D. Doecke, Victor L. Villemagne, Yen Ying Lim, Colin L. Masters, Yan Jiang Wang

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25 Citations (Scopus)

Abstract

The pathological relevance of naturally occurring antibodies to β-amyloid (NAbs-Aβ) in Alzheimer’s disease (AD) remains unclear. We aimed to investigate their levels and associations with Aβ burden and cognitive decline in AD in a cross-sectional cohort from China and a longitudinal cohort from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. NAbs-Aβ levels in plasma and cerebrospinal fluid (CSF) were tested according to their epitopes. Levels of NAbs targeting the amino terminus of Aβ increased, and those targeting the mid-domain of Aβ decreased in both CSF and plasma in AD patients. Higher plasma levels of NAbs targeting the amino terminus of Aβ and lower plasma levels of NAbs targeting the mid-domain of Aβ were associated with higher brain amyloidosis at baseline and faster cognitive decline during follow-up. Our findings suggest a dynamic response of the adaptive immune system in the progression of AD and are relevant to current passive immunotherapeutic strategies.

Original languageEnglish
Article numbereabb0457
Number of pages9
JournalScience Advances
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Jan 2021
Externally publishedYes

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