@article{5986cfb029c94661b5baf3a2b6f7c549,
title = "Testing the link between isoaspartate and Alzheimer's disease etiology",
abstract = "Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts protein structures, making them prone to aggregation. Here we strengthened the link between isoAsp and Alzheimer's disease (AD) by novel approaches to isoAsp analysis in human serum albumin (HSA), the most abundant blood protein and a major carrier of amyloid beta (Aβ) and phosphorylated tau (p-tau) in blood. We discovered a reduced amount of anti-isoAsp antibodies (P < 0.0001), an elevated isoAsp level in HSA (P < 0.001), more HSA aggregates (P < 0.0001), and increased levels of free Aβ (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with Aβ and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of Aβ and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.",
keywords = "Alzheimer's disease (AD), aging, blood analysis, deamidation, enzyme-linked immunosorbent assay (ELISA), human serum albumin (HSA), in vitro diagnostics, mass spectrometry, protein aggregation",
author = "Jijing Wang and Cong Guo and Zhaowei Meng and Zwan, {Marissa D.} and Xin Chen and Sven Seelow and Lundstr{\"o}m, {Susanna L.} and Sergey Rodin and Teunissen, {Charlotte E.} and Zubarev, {Roman A.}",
note = "Funding Information: This work has been supported by China Scholarship Council (KI‐CSC), Horizon 2020 project TopSpec, National Natural Science Foundation of China (Grant 11804218), Zorgonderzoek Nederland medische wetenschappen (ZonMw‐Memorabel, project no. 73305095003; a project in the context of the Dutch Deltaplan Dementie), Gieskes‐Strijbis Foundation, Alzheimer Nederland (Dutch Alzheimer's Society), Hersenstichting (Dutch Brain Foundation), and Ministry of Science and Higher Education of the Russian Federation (agreement no. 075‐15‐2020‐899). Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2022",
doi = "10.1002/alz.12735",
language = "English",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
publisher = "Elsevier",
}