|聯絡電話||+886-2-28267000 ext. 6252|
|POSITION TITLE/AFFILIATIONS||Assistant Researcher/Brain Research Center|
Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance. Although the majority of AD cases are sporadic, about 5% of cases are inherited in an autosomal dominant pattern as familial AD (FAD) and manifest at an early age. Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) gene account for the majority of early-onset FAD. Now we are generating human induced pluripotent stem cells (hiPSCs) derived from AD patients’ blood or fibroblasts harboring the FAD APP or PSEN1 mutation, and double-variant alleles for APOE ε4. Moreover, we will use the latest gene-editing tool, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), to correct gene mutation in AD-iPSCs. Then, we will differentiate these AD-iPSC (with or without gene correction) lines to the neuronal lineage to study whether these neurons have mature phenotypic and physiological properties, as well as AD-like biochemical features. In the future, FAD hiPSCs harboring disease properties can be used as humanized models to test novel diagnostic methods and therapies and explore novel hypotheses for AD pathogenesis.