SpotLight Proteomics Identifies Variable Sequences of Blood Antibodies Specific Against Deamidated Human Serum Albumin

Spontaneous deamidation of asparaginyl residues in proteins, if not repaired or cleared, can set in motion a cascade that leads to deteriorated health. Previously, we have discovered that deamidated human serum albumin (HSA) is elevated in the blood of patients with Alzheimer’s disease and other neurodegenerative diseases, while the level of endogenous antibodies against deamidated HSA is significantly diminished, creating an imbalance between the risk factor and the defense against it. Endogenous antibodies against deamidated proteins are still unexplored. In the current study, we employed the SpotLight proteomics approach to identify novel amino acid sequences in antibodies specific to deamidated HSA. The results provide new insights into the clearance mechanism of deamidated proteins, a possible avenue for prevention of neurodegeneration. [Display omitted] •We purified from healthy blood antibodies specific against deamidated HSA.•SpotLight proteomics uncovered novel isoaspartate-specific antibody sequences.•Antibodies against deamidated HSA may be specific to other aged proteins.•Anti-isoaspartate antibodies may render ways of preventing neurodegeneration. The accumulation of isoaspartate in aged, deamidated blood proteins can lead to deteriorated health, e.g., Alzheimer’s disease. Native antibodies against isoaspartate help maintaining health. We isolated endogenous antibodies against aged human serum albumin and identified novel amino acid sequences in their variable regions. Evidence is found of specificity of these antibodies against other aged proteins. These findings provide new insights into the clearance of aged proteins and indicate a novel possible avenue for prevention and treatment of age-related disorders.