A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

Abstract

Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16–17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population.

PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer’s Disease

“…In terms clinical symptoms, memory loss, visuospatial dysfunction and various neuropsychiatric symptoms, personality changes and speech disturbances were found in proband patient from Family 1. In proband patient of Family 2, memory loss appeared at the age of 37 [ 11 ], with altered mood and marked ideomotor apraxia.…”

“…Proband patient was part of Clinical Research Center for Dementia of South Korea (CREDOS) project, which analyzed APP , PSEN1 and PSEN2 mutations in 100 EOAD patients. Clinical details and scientific predictions were not included in the previously reported study [ 11 ]. In this manuscript, a detailed description of this case with detailed clinical, imaging data, and structure prediction analyses are presented.…”

“… ( a ) Family tree of patient with PSEN1 T116I mutation (Family 1); and ( b ) family tree of patient with PSEN1 T116I mutation (Family 2). This figure was adapted and reprinted with the permission from Dove Medical Press (Clinical Interventions in Aging) [ 11 ]. White circles mean asymptomatic patients, which were not diagnosed with disease.…”

Can Long-Term Regular Practice of Physical Exercises Including Taichi Improve Finger Tapping of Patients Presenting With Mild Cognitive Impairment?

“…There is a considerable risk of MCI developing into dementia, but its progression over time varies tremendously among patients. AD is the most common diagnosis of dementia in elderly persons and is one of the devastating neurodegenerative disorders ( An et al, 2016 ). AD is characterized by progressive loss of memory, thinking, learning, and cognitive ability, aggregation (including extracellular deposition) of the Aβ peptide, and intracellular aggregation of phosphorylated tau protein ( Kim-Ha and Kim, 2016 ).…”

The Role of Genetics in Advancing Precision Medicine for Alzheimer’s Disease—A Narrative Review

“…A recent systematic review of studies from the US, Europe, India, and China shows that the worldwide proportion of EOAD is around 5% of all AD cases ( 39 ). Of note, only 30–60% of EOAD patients have a positive family history for dementia, and about 10–14% have a family history that is consistent with autosomal dominant inheritance ( 40 – 42 ). Thus, in addition to the Mendelian disease presentation of EOAD, a substantial proportion of EOAD cases fall into the category of sporadic and genetically complex disease.…”