A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences.
There 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.
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.
Yat-Fung
YF
Shea
Department of Medicine, LKS Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region; Alzheimer's Disease Research Network, Strategic Research Theme on Aging, The University of Hong Kong, Pok Fu Lam, Hong Kong, Hong Kong Special Administrative Region.
Leung-Wing
LW
Chu
Division of Clinical Biochemistry, Department of Pathology and Clinical Biochemistry, Queen Mary Hospital, Hong Kong, Hong Kong Special Administrative Region.
Angel On-Kei
AO
Chan
Department of Medicine, LKS Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region.
Joyce
J
Ha
Center for Transport Phenomena, Energy Research Institute of Shandong Academy of Sciences, Jinan, People's Republic of China.
Yan
Y
Li
Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, Hong Kong Special Administrative Region.
You-Qiang
YQ
Song
D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D044466:Asian People; D006801:Humans; D009154:Mutation; D010375:Pedigree; D053764:Presenilin-1 / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics*; D013624:Taiwan
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2
amyloid precursor protein; autosomal dominant; familial Alzheimer's disease; presenilin-1; presenilin-2