Pick bodies in a family with presenilin-1 Alzheimer's disease.
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.
Halliday
Glenda M
GM
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
Song
Yun Ju C
YJ
Lepar
Gila
G
Brooks
William S
WS
Kwok
John B
JB
Kersaitis
Cindy
C
Gregory
Gillian
G
Shepherd
Claire E
CE
Rahimi
Farid
F
Schofield
Peter R
PR
Kril
Jillian J
JJ
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
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D008715:Methionine; D007930:Leucine