Brain β-spectrin is a component of senile plaques in Alzheimer's disease

Spectrin is a multifunctional cortical membrane skeleton protein. We report here that the β-subunit of spectrin is an integral component of β-amyloid plaques in Alzheimer's disease (AD). We prepared anti-β-spectrin antibodies by using synthetic peptides corresponding to the N-terminal and C-terminal domains of β-spectrin variants. When tissues from post-mortem AD brains were immunostained with these domain-specific affinity purified β-spectrin antibodies, β-amyloid plaques were specifically stained in the cortical parenchyma in approximately one third of the cases. The staining was unaffected by preadsorption of β-spectrin antibodies with A₄/β_1–40 peptide. The sodium dodecyl sulfate-insoluble amyloids were also stained by the β-spectrin antibodies. The anti-α-spectrin antibody stained neuronal processes, but not amyloid plaques. The presence of β-spectrin in the amyloid plaques in a subset of sporadic AD cases suggests that distinct biochemical pathways are involved in the formation or deposition of β-amyloid plaques, and that an abnormality of β-spectrin structure or function may be involved in the formation or deposition of β-amyloid plaques in this subset of AD cases.