Processing of presenilin 1 in brains of patients with Alzheimer's disease and controls.
Mutations in the presenilin genes are involved in the aetiology of the majority of familial early-onset Alzheimer disease (AD) cases. Presenilin 1 (PS1) is proteolytically processed in vivo, resulting in the accumulation of N-terminal approximately 27-28 kDa and C-terminal approximately 18 kDa derivatives. To examine the metabolism of PS1 in brains of patients with AD harbouring PS1 mutations I143T and G384A, we performed immunoblot analyses of brain homogenates using well characterized antibodies. We document that approximately 27-28 kDa N-terminal and approximately 18 kDa C-terminal PS1 proteolytic fragments accumulate in brain of these individuals, and that in large part the accumulation pattern is indistinguishable from that observed in brains from individuals with sporadic AD or controls. Notably, little, if any, full-length PS1 was detected in brain tissue of patients carrying PS1 mutations or in those with sporadic AD, indicating that failed proteolysis of PS1 is not a central feature of pathogenesis in these patients.
Hendriks
L
L
Department of Biochemistry, Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, University of Antwerp, Belgium.
Thinakaran
G
G
Harris
C L
CL
De Jonghe
C
C
Martin
J J
JJ
Sisodia
S S
SS
Van Broeckhoven
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D053764:Presenilin-1
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1