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.
Sihag
R K
RK
Department of Psychiatry, Harvard Medical School, Belmont, MA, USA. sihag@codon.nih.gov
Cataldo
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AM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000918:Antibody Specificity; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000276:immunology; D017434:Protein Structure, Tertiary; D013049:Spectrin / Q000032:analysis* / Q000276:immunology; D013194:Staining and Labeling / Q000379:methods
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D013049:Spectrin