American Journal of Medical Genetics Part B: Neuropsychiatric Genetics | February 13, 2021

Hsu JL, Lin CH, Chen PL, Lin KJ and Chen TF

Am J Med Genet B Neuropsychiatr Genet. 2021

DOI: https://doi.org/10.1002/ajmg.b.32836

Abstract

Recent genetic progress allows the molecular diagnosis of young‐onset dementia, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We aimed to identify the mutational and clinical spectra of causal genes in a Taiwanese cohort of young‐onset dementia. Ninety‐one patients with young‐onset dementia and 22 age/gender‐matched controls were recruited. Genetic causes were identified by a targeted panel containing 90 causative genes for AD, FTD, and related neurodegenerative disorders. Plasma biomarkers, including total tau, Aβ42, and Aβ40, were assayed. Molecular amyloid and tau PET scans were performed in some patients carrying mutations. Nine of 52 patients (17.3%) with young‐onset AD had mutations: 2 (22.2%), 4 (44.5%), 2 (22.2%), and 1 (11.1%) in APP, PSEN1, PSEN2, and TREM2, respectively. Two of 33 patients (6.1%) with young‐onset FTD had mutations in MAPT and LRRK2. Three of the 6 patients (50.0%) with possible FTD combined with other neurodegenerative disorders had individual mutations in APP, PSEN2, or MAPT. Patients with PSEN1 mutations had earlier onset of disease than those without mutations (p = .02). Plasma level of total tau was increased and Aβ42 and Aβ40 levels decreased in all groups of dementia patients compared to controls. Our findings provide a genetic spectrum of young‐onset dementia in our population.