title: Comparison of Abeta levels in the brain of familial and sporadic Alzheimer's disease.
abstract: Mutations in presenilin (PS) and amyloid precursor protein (APP) genes are a predominant cause for early-onset familial Alzheimer disease (AD). Although these mutations are rare, they have in the past decades advanced our understanding of the underlying molecular mechanisms of AD. In the present study, Abeta levels were measured in cortical regions of APPsw and PS1 (M146V) mutation carriers, sporadic AD (SAD) and age-matched non-demented individuals. We found similar levels of soluble Abeta42, insoluble and soluble Abeta40 in both APPsw mutation carriers and SAD. However, lower levels of insoluble Abeta42 were detected in the frontal and temporal cortex of APPsw brain. In PS1 brain, insoluble Abeta40 and Abeta42 levels were significantly lower in all four cortical regions compared with SAD, whilst levels of Abeta40 were lower in frontal and occipital cortex compared with APPsw brain. The insoluble Abeta42/40 ratio was similar in SAD and APPsw but significantly higher in PS1 mutation carriers. Our results indicate that the pattern of Abeta deposition in PS1 mutation carriers differs from that in both APPsw and SAD, whereas the pattern in APPsw mutation carriers is more similar to that in SAD.
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Alzheimer Neurobiology, Sweden. ewa.hellstrom-lindahl@ki.se
authors.forename: E
authors.initials: E
authors.lastname: Hellström-Lindahl
authors.forename: M
authors.initials: M
authors.lastname: Viitanen
authors.forename: A
authors.initials: A
authors.lastname: Marutle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)