P1–304: Fine mapping of 12p for memory traits: A complementary approach to understanding the genetics of Alzheimer's disease
Year: 2006
Type: article
Study design: Observational Study
Abstract: Studies have implicated 12p as a candidate region for Alzheimer's disease (AD) gene(s), including our AD genome scan. This region includes multiple candidate genes, such as CNAP1, GAPD, and A2M. To examine the relations among memory traits (endophenotypes), AD, and three genes from 12p: CNAP1, GAPD, and A2M. We studied 1068 individuals from 210 Caribbean Hispanic families with late–onset AD. We administered a battery of neuropsychological tests to assess memory, abstract reasoning, language and visuospatial functions in both affected and unaffected family members. Here, we focus on three verbal and one nonverbal memory test: delayed recall, delayed recognition, long–term storage, and visual memory. We conducted a family–based association analysis using all family members, controlling for age, sex, and education. We then repeated the analysis using unaffected individuals only, to assess the effects of these genes on memory performance in unaffecteds. Among affected and unaffected family members, CNAP1 and GAPD were significantly associated with verbal memory, but A2M was not. For delayed recognition, a sensitive predictor of AD, we observed a strong association with CNAP1 (rs740850, p=0.0071) and GAPD (rs3741918, P=0.0190; rs1060620, p=0.0293; rs1060619, p=0.0308). These SNPs were also significantly associated when AD was used as the phenotype. In contrast, these SNPs were not significantly associated with long–term storage and the Benton recognition test. To differentiate genetic effects on memory vs. AD, we repeated the analyses using unaffecteds only. Among unaffecteds, CNAP1 and GAPD were no longer associated with delayed recognition, but A2M was (p=0.0126). None of the SNPs were significantly associated with delayed recall and long–term storage among unaffecteds. We show that we can use memory traits to better understand the genetics of AD. CNAP1 and GAPD were significantly associated with verbal memory and AD, but not with visual memory and long–term storage. These genes may contribute to AD via verbal memory. A2M was not associated with either verbal memory or AD in these families, but was associated with delayed recognition and Benton recognition in unaffecteds only. Further studies are needed.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2582758532