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

Spectrin is a multifunctional cortical membrane skeleton protein. We report here that the beta-subunit of spectrin is an integral component of beta-amyloid plaques in Alzheimer's disease (AD). We prepared anti-beta-spectrin antibodies by using synthetic peptides corresponding to the N-terminal and C-terminal domains of beta-spectrin variants. When tissues from post-mortem AD brains were immunostained with these domain-specific affinity purified beta-spectrin antibodies, beta-amyloid plaques were specifically stained in the cortical parenchyma in approximately one third of the cases. The staining was unaffected by preadsorption of beta-spectrin antibodies with A4/beta 1-40 peptide. The sodium dodecyl sulfate-insoluble amyloids were also stained by the beta-spectrin antibodies. The anti-alpha-spectrin antibody stained neuronal processes, but not amyloid plaques. The presence of beta-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 beta-amyloid plaques, and that an abnormality of beta-spectrin structure or function may be involved in the formation or deposition of beta-amyloid plaques in this subset of AD cases.