P4‐050: TOMM40 Variable Length Polymorphism is Associated With Memory Function in Asymptomatic Middle‐aged Persons
Year: 2010
Type: article
Study design: Observational Study
Abstract: A TOMM40 polymorphism, a variable length intronic poly T repeat (rs10524523), has been shown to influence age of Alzheimer's disease (AD) onset. In this study, we tested the hypothesis that subjects homozygous for TOMM40 short poly T sequences <21 (SPT) would show better performance on measures of learning and memory than those who were homozygous for longer poly T sequences ≥21 (LPT) in middle-aged subjects with a family history of AD. The study population includes 726 middle-aged asymptomatic persons enrolled in the Wisconsin Registry for Alzheimer's Prevention (WRAP) who had been genotyped for APOE and TOMM40. A total of 129 were homozygous for SPT sequences <21 (low risk) and 229 were homozygous for LPT sequences ≥21 (high risk). Study groups were defined by TOMM40 genotyping based on the length of the poly T sequences regardless of APOE genotype. Serial position profiles and total learning on the Rey Auditory Verbal Learning Test (AVLT) were compared between groups controlling for age, gender and education. The mean age of the study population was 54 and 69% were female. There were no significant age, gender or education differences between SPT and LPT groups. The two TOMM40 groups differed significantly in total words learned on the AVLT (p = .012) with the LPT TOMM40 group remembering fewer words. There were significant differences in the serial position curve with significantly poorer recall from the primacy region on the AVLT (p = .001). Nineteen percent of the SPT group had an APOE ε4 compared with 55% of the LPT group. When APOE genotype (ε4 carrier vs. non-carrier) was added to the model, TOMM40 remained significant on both measures. Longer TOMM40 poly T sequence length was associated with differences in memory and learning that are seen in early AD. These changes were seen in middle-aged asymptomatic persons, suggesting that TOMM40 genotyping may prove useful in stratifying persons at different levels of AD risk in studies of pre-symptomatic AD. The role that TOMM40 plays in AD pathogenesis and its relationship to APOE genotype as a genetic risk factor for AD remain to be determined.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1983795121