Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Abstract

Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.

Gene mutations in a Han Chinese Alzheimer's disease cohort

“…has been reported three times. The other three p.L226F families showed an early-onset (33-37 years), AD or FTD-like symptoms, and biopsy-proved AD (Bagyinszky, Park, et al, 2016;Bagyinszky, Youn, et al, 2016). As compared to the reported L226F families, the p.L226R family in the current study had a later age of onset and similar language impairment as the first symptom; however, no Parkinsonism-like syndrome was observed during the disease.…”

“…The other three p.L226F families showed an early-onset (33-37 years), AD or FTD-like symptoms, and biopsy-proved AD (Bagyinszky, Park, et al, 2016;Bagyinszky, Youn, et al, 2016). The other three p.L226F families showed an early-onset (33-37 years), AD or FTD-like symptoms, and biopsy-proved AD (Bagyinszky, Park, et al, 2016;Bagyinszky, Youn, et al, 2016).…”

“…In addition, the PSEN1 p.L226R mutation (Coleman, Kurlan, Crook, Werner, & Hardy, 2004) (Bagyinszky, Park, et al, 2016;Bagyinszky, Youn, An, & Kim, 2016;Coleman et al, 2004;Gomez-Tortosa et al, 2010;Zekanowski et al, 2006), while p.L226F…”

Motoric Cognitive Risk Syndrome: Association with Incident Dementia and Disability

“…Few studies based in Japanese cohorts have investigated prevalence and etiologies of MCR [4,5], but the risk of incident dementia associated with MCR in Japan has not been reported [1]. Due to potential biological differences between races, e.g., genetic pattern related to dementia [6], it is important to examine the etiology of MCR and its association with dementia in different countries to obtain biological insights and to develop global dementia preventive strategies.…”

Pathogenic PSEN1 Glu184Gly Mutation in a Family from Thailand with Probable Autosomal Dominant Early Onset Alzheimer’s Disease

“…Patients with young onset AD presented a very aggressive phenotype and rapid disease progression. Additional symptoms, such as Parkinsonism, epilepsy, and language and behavioral impairment may also be prominent in EOAD [17]. Interestingly, de novo cases of AD mutations were also reported without prior family history or any affected family members [2,[18][19][20].…”