Testing the link between isoaspartate and Alzheimer's disease etiology

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 (A beta) 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 A beta (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with A beta and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of A beta and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.

Automated summary

This study strengthens the association between isoAsp and Alzheimer's disease (AD) using novel approaches to isoAsp analysis in blood samples. The findings demonstrate elevated isoAsp levels, reduced anti-isoAsp antibodies, increased A beta concentration, and more protein aggregation in AD blood compared to controls. Additionally, deamidation reduces the binding capacity of blood protein HSA with A beta and p-tau.