Presenilin immunoreactivity in Alzheimer's disease.
The role of presenilin (PS) mutations in familial Alzheimer's disease (AD) may be as a toxic gain of function, but in sporadic disease their contribution is more difficult to understand. In this study, we investigated PS proteins in sporadic AD by comparing the immunocytochemical profiles in sporadic AD with control brains using a quantitative immunocytochemical approach to both the N- and C-terminals of PS1 and PS2. Ten patients with pathologically proven AD (using modified Consortium to Establish a Registry for Alzheimer's Disease [CERAD] criteria) and 10 controls were age- and sex-matched. The immunocytochemical primary antibodies were affinity-purified goat polyclonal antibodies and the secondary antibodies were biotinylated donkey anti-goat to the N- and C-terminal of both PS1 and PS2. The number of PS-containing neurones was quantified manually and without the knowledge of the diagnosis. We found no significant differences in the number of PS1- and PS2-containing neurones in three anatomical regions for both N- and C-terminals between AD and controls. Our findings argue in favour of functional changes in PS molecules contributing to the pathogenesis of AD and are consistent with the hypothesis of dysfunction of the entire gamma-secretase complex, of which PS proteins are a constituent.
Panegyres
P K
PK
Neuregene, Mount Medical Centre, Perth, WA, Australia. macfarlane4@optusnet.com.au
Toufexis
K
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D053764:Presenilin-1; D053766:Presenilin-2; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2