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.
To analyze the FTD genes in the DNA samples of patients belonging to families clinically classified as probable Alzheimer's disease (FAD) in the early 1990s and not carrying mutation in the three main genes linked to FAD (Presenilin 1, Presenilin 2, and Amyloid precursor protein).
Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD).
We examine the significance of the "fAD mutation reading frame preservation rule" that applies to PSEN1 and PSEN2 (and AβPP) and look at alternative roles for AβPP and Aβ in fAD.
Thus missense, splice site or duplication mutants in the presenilin 1 (PS1), presenilin 2 (PS2) or the amyloid precursor protein (APP) genes, which alter the levels or shift the balance of Aβ produced, are associated with rare, highly penetrant autosomal dominant forms of Familial Alzheimer's Disease (FAD).
Of nearly 200 PRESENILIN mutations causing early onset, familial Alzheimer's disease (FAD) only the K115Efx10 mutation of PSEN2 causes truncation of the open reading frame.
Mutations in PS1, PS2, and Aβ protein precursor are involved in the etiology of familial Alzheimer's disease (FAD), while the cause of the sporadic form of AD (SAD) is still not known.
Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein (APP) genes cause familial Alzheimer's disease (FAD) in a nearly fully penetrant, autosomal dominant manner, providing a unique opportunity to study presymptomatic individuals who can be predicted to develop Alzheimer's disease (AD) with essentially 100% certainty.
We reported a patient with early-onset FAD and the PSEN2p.Met239Ile mutation, presenting with severe executive dysfunction and myoclonic tremor, associated with memory loss.
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.
Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease--that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes.
The subcellular localization of presenilin-1 (PS1) and presenilin-2 (PS2), two proteins that, when mutated, cause familial Alzheimer's disease (AD), is controversial.
Mutations of three different genes, encoding β-amyloid precursor protein (APP), presenilin 1 and presenilin 2 are associated with familial Alzheimer's disease (AD).