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- Yat-Fung Shea, Leung-Wing Chu, Angel On-Kei Chan, Joyce Ha, Yan Li, and You-Qiang Song.
- Department of Medicine, LKS Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region. Electronic address: syf321@ha.org.hk.
- J Formos Med Assoc. 2016 Feb 1; 115 (2): 677567-75.
AbstractThere are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p < 0.001) and were more commonly affected by seizures, spastic paraparesis, myoclonus, and cerebellar signs (p < 0.001, p < 0.001, p = 0.003, and p = 0.002, respectively). Patients with PSEN2 mutations have a delayed AOO with longest disease duration and presented more frequently with disorientation (p = 0.03). Patients with amyloid precursor protein (APP) mutations presented more frequently with aggression (p = 0.02) and those with APP duplication presented more frequently with apraxia (p = 0.03). PSEN1 mutations before codon 200 had an earlier AOO than those having mutations after codon 200 (41.4 ± 8.0 years vs. 44.7 ± 8.7 years, p < 0.001). Because 42.9% of the mutations reported are novel, the mutation spectrum and clinical features in Asian FAD families could be different from that of whites. Asian patients with PSEN1 mutations presented more frequently with disorientation (p = 0.02) and personality change (p = 0.01) but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites.Copyright © 2015. Published by Elsevier B.V.
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