Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling.
Mutations of three different genes-amyloid precursor protein (APP), presenilin 1 (PS-1), presenilin 2 (PS-2)-have been found in early-onset autosomal dominant forms of AD, of the human microtubule associated-protein tau gene (MAPT) in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), of the BRI gene in familial British dementia, of the PI12 gene in familial encephalopathy with neuroserpin inclusion bodies.
Mutations in presenilin-1 (PSEN1) cause autosomal dominant Alzheimer's disease and mutations in MAPT cause the familial tauopathy Frontotemporal dementia linked to chromosome 17 (FTDP-17).
MOCA is an integrator of the neuronal death signals that are activated by familial Alzheimer's disease-related mutants of amyloid β precursor protein and presenilins.
Interestingly, two presenilin 1 (PS1) mutations (Leu113Pro and insArg352) recently have been associated with familial FTD albeit without neuropathological confirmation.
Human presenilin-1, but not familial Alzheimer's disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing.
Genetic testing confirmed the absence of mutations in the presenilin 1 gene in 1 patient; subsequent testing revealed the R406W tau mutation in both individuals leading to a diagnosis of frontotemporal dementia [F]FDDNP retention broadly correlated with CSF levels of t-tau and p-tau.