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[P2–127]: HIGH FREQUENCY OF ABCA7 MUTATIONS IN PATIENTS WITH EARLY‐ONSET ALZHEIMER's DISEASE
Author(s) -
Van Giau Vo,
Bagyinszky Eva,
Shim Kyu Hwan,
Yang Youngsoon,
Youn Young Chul,
An Seong Soo,
Kim Sang Yun
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.777
Subject(s) - missense mutation , early onset alzheimer's disease , genetics , presenilin , allele , exome sequencing , mutation , biology , medicine , gene , alzheimer's disease , disease
Background:Alzheimer Disease (AD) genomics, including the AD Sequencing Project (ADSP) and the AD Genetics Consortium (ADGC) have focused on non-Hispanic White populations. Puerto Ricans, constituting over 1.5% of the US population and the second largest Hispanic population in the continental US, have an estimated AD prevalence of 65,000. However, there has been limited study of AD genetics in this group. Understanding the genetic causes of AD in multiple ethnic groups will lead to better diagnosis, prevention and treatment. For this abstract we will describe our large cohort of well-phenotyped Hispanics with AD from Puerto Rico, a large number being from multiplex AD families. Methods: Eligible multiplex families have at least two living family members with AD as well as one elderly family member who is cognitively intact (CI). Each individual with AD who was enrolled had a confirmed AD diagnosis by a neurologist and was assess by our research battery consisting of neurological exams and imaging. We will describe our cohort based on current ascertainment numbers stratified by diagnosis, family structure, age at onset (AAO), and APOE status. In addition, we provide preliminary 3MS findings. Results: This cohort consists of 306 individuals (68% female; mean age1⁄4 78 years) from 149 families. We have enrolled 128 individuals with AD, 174 CI individuals, and four individuals with Mild Cognitive Impairment (MCI). Among the 128 individuals with AD, 97% are classified as LOAD; the remaining 3% are EOAD. Forty-one (of 149 families) are multiplex from which 122 individuals were sampled. Within these 122 individuals, 49%meet criteria for LOAD and 51% are CI. Among the multiplex families, the mean number of LOAD cases per family is 2.7; 11 families contained four AD living individuals. The entire cohort was genotyped for APOE; 42% of the sample carries one e4 allele and 6.5% are homozygous. Among the e4/e4 homozygous individuals, 60% were AD cases vs. 40% who were CI. Conclusions:This resource will complement ongoing next-generation sequencing efforts such as the ADSP and ADGC, and will allow identification of novel risk and protective variants specific to Hispanic populations.