PRESENCE OF NONFIBRILLAR AMYLOID-BETA PROTEIN IN SKIN BIOPSIES OF ALZHEIMERS-DISEASE (AD), DOWNS-SYNDROME AND NON-AD NORMAL PERSONS

A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's syndrome (DS) and from persons without AD were used in this study. The age range was from 7 to 89 years. Positive immunoreactivit y of skin biopsies to monoclonal antibody 4G8, which is reactive to am ino acid residue 17-24 of synthetic amyloid beta protein (A beta), and 4G8-Fab (the antigen-binding fragment of 4G8 IgG, reactive only to am yloid plaque) was observed in the epidermis-dermis junction or the bas ement membrane of the epidermis and in some blood vessels of the biops y skins of 13/18 (72%) AD, 9/10 (90%) DS, and 14/38 (37%) non-AD contr ol cases. The Fisher exact probability test revealed a significant dif ference (P=0.0415 one-tailed) in immunoreactivity between AD and age-m atched controls. There was also a significant difference (P=0.0152 one -tailed; P=0.0200 two-tailed) between DS and age-matched control in th e same test. Immune-gold electron microscopy examination of these case s with positive immunoreactivity revealed that the gold particles were deposited along the basement membrane of the epidermis. Amyloid fibri ls were not observed in the regions with gold particles. Results of th is study suggest that A beta is associated with the basement membrane of skin and is present in amorphous, non-fibrillar form as soluble A b eta.