96, 1391-1396) suggests that it is a regulated physiological event that also occurs in the absence of the familial Alzheimer's disease-associated mutations in PS2.
FAD-associated mutations in PS1 and PS2 do not significantly modify either their migration patterns on SDS-polyacrylamide gel electrophoresis or their overall subcellular localization, although subtle differences in perinuclear staining were noted for mutant PS1.
presenilin-2 is one of the causative genes for familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor for late-onset and sporadic early-onset Alzheimer's disease.
A mutational analysis of APP, PS1, and PS2 genes can be used for both symptomatic and presymptomatic genetic testing and counselling in familial Alzheimer's disease (FAD).
Although some investigators have shown that mutant PS1 processing is unaltered (with the exception of PS1-deltaE9, which lacks the cleavage site) in stably transfected cells and PS1-FAD transgenic mice, other investigators have reported altered FAD mutant PS1 and PS2 protein processing in transiently transfected cells and human FAD patients.
At least half of all cases of early onset (<60) familial Alzheimer's disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2).
Autosomal dominant forms of familial Alzheimer's disease (FAD) are caused by mutations of the amyloid precursor protein (APP) gene and by mutations of the genes encoding for presenilin 1 or presenilin 2.
By generating novel tools for measuring Ca<sup>2+</sup> in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca<sup>2+</sup> signaling and brain network activity, as summarized below.
Early onset familial Alzheimer's disease (FAD) is linked to autosomal dominant mutations in the amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2) genes.
Established genetic causes of familial Alzheimer disease (AD) involve genes for beta-amyloid precursor protein (betaAPP), presenilin-1, and presenilin-2.
Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2).
Here we generate iPSCs from fibroblasts of FAD patients with mutations in PS1 (A246E) and PS2 (N141I), and characterize the differentiation of these cells into neurons.
In familial Alzheimer's disease, Abeta is excessively produced and deposited because of mutations in the amyloid precursor protein, presenilin-1, and presenilin-2 genes.