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American Journal of Pathology, Vol 149, 1839-1846, Copyright © 1996 by American Society for Investigative Pathology

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Antibodies to presenilin proteins detect neurofibrillary tangles in Alzheimer's disease

GM Murphy Jr, LS Forno, WG Ellis, D Nochlin, E Levy-Lahad, P Poorkaj, TD Bird, Z Jiang and B Cordell
Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, California, USA.

Mutations in the presenilin (PS)-1 and PS-2 genes have been shown to be linked with the development of Alzheimer's disease (AD). We examined Alzheimer's brain tissue by immunohistochemistry using a set of antibodies raised to sequences shared between PS-1 and PS-2 proteins. These antibodies reacted exclusively with a subset of neurofibrillary tangles and not with neuropil threads or dystrophic neurites. Detection of the presenilin epitope in neurofibrillary tangles was observed in sporadic Alzheimer's disease brain samples and in samples from individuals carrying PS-1 and PS-2 mutations with no qualitative difference. These data indicate that both wild-type and mutant PS proteins are involved in a common pathogenic pathway in AD.

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