Distinguishable effects of Presenilin-1 and APP717 mutations on amyloid plaque deposition

Both APP and PS-1 are causal genes for early-onset familial Alzheimer's dis ease (AD) and their mutation effects on cerebral A beta deposition in the s enile plaques were examined in human brains of 29 familial AD (23 PS-1, 6 A PP) cases and 14 sporadic AD cases in terms of A beta 40 and A beta 42. A b eta isoform data were evaluated using repeated measures analysis of varianc e which adjusted for within-subject measurement variation and confounding e ffects of individual APP and PS-1 mutations, age at onset, duration of illn ess and APOE genotype. We observed that mutations in both APP and PS-1 were associated with a significant increase of A beta 42 in plaques as been doc umented previously. In comparison to sporadic AD cases, both APP717 and PS- 1 mutation cases had an increased density (measured as the number of plaque s/mm(2)) and area (%) of A beta 42 plaques. However, we found an unexpected differential effect of PS-1 but not APP717 mutation cases. At least some o f PS-1 but not APP717 mutation cases had the significant increase of densit y and area of A beta 40-plaques as compared to sporadic AD independently of APOE genotype. Our results suggest that PS-1 mutations affect cerebral acc umulation of A beta burden in a different fashion from APP717 mutations in their familial AD brains. (C) 2001 Elsevier Science Inc. All rights reserve d.