title: Distinguishable effects of presenilin-1 and APP717 mutations on amyloid plaque deposition.
abstract: Both APP and PS-1 are causal genes for early-onset familial Alzheimer's disease (AD) and their mutation effects on cerebral Abeta deposition in the senile plaques were examined in human brains of 29 familial AD (23 PS-1, 6 APP) cases and 14 sporadic AD cases in terms of Abeta40 and Abeta42. Abeta isoform data were evaluated using repeated measures analysis of variance which adjusted for within-subject measurement variation and confounding effects of individual APP and PS-1 mutations, age at onset, duration of illness and APOE genotype. We observed that mutations in both APP and PS-1 were associated with a significant increase of Abeta42 in plaques as been documented previously. In comparison to sporadic AD cases, both APP717 and PS-1 mutation cases had an increased density (measured as the number of plaques/mm(2)) and area (%) of Abeta42 plaques. However, we found an unexpected differential effect of PS-1 but not APP717 mutation cases. At least some of PS-1 but not APP717 mutation cases had the significant increase of density and area of Abeta40-plaques as compared to sporadic AD independently of APOE genotype. Our results suggest that PS-1 mutations affect cerebral accumulation of Abeta burden in a different fashion from APP717 mutations in their familial AD brains.
authors.affiliation: Department of Molecular Biology, Tokyo Institute of Psychiatry, Tokyo, Japan
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: C
authors.initials: C
authors.lastname: Lippa
authors.forename: T
authors.initials: T
authors.lastname: Tomiyama
authors.forename: F
authors.initials: F
authors.lastname: Miyatake
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.forename: A
authors.initials: A
authors.lastname: Tamaoka
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.forename: S
authors.initials: S
authors.lastname: Shoji
authors.forename: L E
authors.initials: LE
authors.lastname: Nee
authors.forename: D A
authors.initials: DA
authors.lastname: Pollen
authors.forename: P H
authors.initials: PH
authors.lastname: St  George-Hyslop
authors.forename: K
authors.initials: K
authors.lastname: Ii
authors.forename: T
authors.initials: T
authors.lastname: Ohtake
authors.forename: R N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: M N
authors.initials: MN
authors.lastname: Rossor
authors.forename: P L
authors.initials: PL
authors.lastname: Lantos
authors.forename: N J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: L A
authors.initials: LA
authors.lastname: Farrer
authors.forename: H
authors.initials: H
authors.lastname: Mori
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D002452:Cell Count; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D053764:Presenilin-1
chemical_list: C094559:APP717; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)