We conclude that altered C99 interactions are a common feature of diverse types of PS1FAD mutants and that also patients with Aβ43-generating FAD mutations could in principle be treated by GSMs.
Familial Alzheimer's disease (FAD) mutations within the catalytic subunit protein of presenilin 1 (PS1) decrease γ-cleavage, resulting in the generation of toxic, long Aβs.
Generation of one iPSC line (IMEDEAi006-A) from an early-onset familial Alzheimer's Disease (fAD) patient carrying the E280A mutation in the PSEN1 gene.
To test this, we isolated EVs from iPSC-derived neuronal cultures generated from an fAD patient harboring a A246E mutation to presenilin-1 and stereotactically injected these EVs into the hippocampi of wild-type C57BL/6 mice.
These findings demonstrate that in mice expressing FAD-linked PS1, microglia play a critical role in the regulation of EE-dependent AHNPC proliferation and neurogenesis and the modulation of affective behaviors.<b>SIGNIFICANCE STATEMENT</b> Inheritance of mutations in genes encoding presenilin 1 (PS1) causes familial Alzheimer's disease (FAD).
Single-point mutations in the genes coding for amyloid precursor protein (APP) and presenilin 1 (PS1), the active subunit of γ-secretase that cleaves APP to produce Aβ, are the main causes of rare but severe familial Alzheimer's disease (fAD).
Mutations in the presenilin1 (PSEN1) cause familial Alzheimer's disease (FAD), providing a special opportunity to study pre-symptomatic individuals who would be predicted to develop Alzheimer's disease (AD) in the future.
These data suggest that in the FADPS1ΔE9 cells, the elevated cellular cholesterol level contributes to the altered APP processing by increasing APP localized in lipid rafts.
Mutations in the presenilin 1 (PS1) gene are a major trigger of familial Alzheimer's disease (AD), yet the mechanisms affected by mutated PS1 causing cognitive decline are not yet elucidated.
Autosomal-dominant familial Alzheimer disease (AD) is caused by by variants in presenilin 1 (<i>PSEN1</i>), presenilin 2 (<i>PSEN2</i>), and amyloid precursor protein (<i>APP</i>).
Generation and characterization of human induced pluripotent stem cell lines from a familial Alzheimer's diseasePSEN1A246E patient and a non-demented family member bearing wild-type PSEN1.
Brains from different transgenic strains and ages developed overt cerebral Aβ deposition, including the β-amyloid precursor protein and presenilin 1 double-transgenic (APP/PS1) mice at ~ 14 months of age, the five familial Alzheimer's disease mutations transgenic (5×FAD) mice at ~ 8 months, the triple-transgenic Alzheimer's disease (3×Tg-AD) mice at ~ 22 months, and aged monkeys (Macaca mulatta and Macaca fascicularis) were examined.
Gene mutations within amyloid precursor protein (APP or AβPP) and/or presenilin 1 (PS1) genes are determinants of familial Alzheimer's disease (fAD) and remain fundamental for experimental models.
Presenilin 1 (PS1) expression in human brain gradually decreases with age and its mutations account for the most common cases of early-onset familial Alzheimer's disease (FAD).