title: Pick bodies in a family with presenilin-1 Alzheimer's disease.
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.
authors.affiliation: Prince of Wales Medical Research Institute and the University of New South Wales, Barker Street, Randwick, Sydney, 2031 NSW, Australia. g.halliday@unsw.edu.au
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Yun Ju C
authors.initials: YJ
authors.lastname: Song
authors.forename: Gila
authors.initials: G
authors.lastname: Lepar
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.forename: John B
authors.initials: JB
authors.lastname: Kwok
authors.forename: Cindy
authors.initials: C
authors.lastname: Kersaitis
authors.forename: Gillian
authors.initials: G
authors.lastname: Gregory
authors.forename: Claire E
authors.initials: CE
authors.lastname: Shepherd
authors.forename: Farid
authors.initials: F
authors.lastname: Rahimi
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Kril
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007930:Leucine / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000378:metabolism; D020774:Pick Disease of the Brain / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D011180:Postmortem Changes; D053764:Presenilin-1; D016875:tau Proteins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D008715:Methionine; D007930:Leucine