Abstract
Presenilin-1 (PS-1) mutations can cause Pick's disease without evidence of Alzheimer's disease (AD). We describe a family with a PS-1 M146L mutation and both Pick bodies and AD. Sarkosyl-insoluble hyperphosphorylated tau showed three bands consistent with AD, although dephosphorylation showed primarily three-repeat isoforms. M146L mutant PS-1 may predispose to both Pick's disease and AD by affecting multiple intracellular pathways involving tau phosphorylation and amyloid metabolism.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Alzheimer Disease / complications
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism*
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Blotting, Western / methods
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DNA Mutational Analysis
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Family Health
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Female
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Genetic Predisposition to Disease
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Humans
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Immunohistochemistry / methods
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Leucine / genetics
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Methionine / genetics
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Middle Aged
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Mutation
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Neurofibrillary Tangles / metabolism
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Pick Disease of the Brain / complications
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Pick Disease of the Brain / genetics
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Pick Disease of the Brain / metabolism*
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Plaque, Amyloid / metabolism
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Postmortem Changes
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Presenilin-1
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tau Proteins / metabolism
Substances
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Membrane Proteins
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PSEN1 protein, human
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Presenilin-1
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tau Proteins
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Methionine
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Leucine