Testing the link between isoaspartate and Alzheimer's disease etiology

Jijing Wang, Cong Guo, Zhaowei Meng, Marissa D. Zwan, Xin Chen, Sven Seelow, Susanna L. Lundström, Sergey Rodin, Charlotte E. Teunissen, Roman A. Zubarev*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
JournalAlzheimer's and Dementia
Early online date2022
Publication statusE-pub ahead of print - 2022

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