Presenilin-2 (PSEN2) mutation is one of the pathogenic factors of autosomal dominant early-onset Alzheimer's disease (EOAD). We generated a human induced pluripotent stem cell (iPSC) line from fibroblasts of an EOAD patient carrying PSEN2 mutation (c.716 T > C) utilizing Sendai reprogramming kit. The resulting iPSC line carried patient-specific point mutation, exhibited typical iPSC morphology, retained a normal karyotype, expressed pluripotency markers, and could form embryoid bodies. Established iPSC line serve as valuable resource for EOAD disease pathogenesis modelling and drug screening.
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Identification and characterization of variants in PSEN1, PSEN2, and APP genes in Chinese patients with early-onset Alzheimer's disease.
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Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
Variants in PSEN1, PSEN2, and APP are major genetic causes of early-onset Alzheimer's disease (EOAD). Our study aimed to identify the genotypic and phenotypic spectrums in a Chinese EOAD cohort and confirm their pathogenicity by functional analysis. This study included 304 unrelated clinically diagnosed EOAD participants of Chinese Han ancestry.
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Division of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Aims: Alzheimer's disease (AD) is a leading cause of dementia, with increasing prevalence. Mutations in genes like MAPT, PSEN1, and PSEN2 are risk factors, leading to the development of several AD model mice. Recent hypotheses suggest AD brain pathology involves abnormal neurodevelopment, decreased pH, and neural hyperexcitation.
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Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, Turin, 10126, Italy.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with both genetic and environmental factors contributing to its pathogenesis. While early-onset AD has well-established genetic determinants, the genetic basis for late-onset AD remains less clear. This study investigates a large Italian family with late-onset autosomal dominant AD, identifying a novel rare missense variant in GRIN2C gene associated with the disease, and evaluates the functional impact of this variant.
View Article and Find Full Text PDFIntegrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.
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Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.
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Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.
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Laboratory for Membrane Trafficking, VIB Center for Brain and Disease Research, Leuven, Belgium.
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