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.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Keyword

aging

Alzheimer's disease (AD)

blood analysis

deamidation

enzyme-linked immunosorbent assay (ELISA)

human serum albumin (HSA)

in vitro diagnostics

mass spectrometry

protein aggregation

Publication and Content Type

ref (subject category)

art (subject category)