Heritability of Different Forms of Memory in the Late Onset Alzheimer's Disease Family Study

Article type: Research Article

Authors: Wilson, Robert S.^{a; b; c; *} | Barral, Sandra^{d; f} | Lee, Joseph H.^{d; e; h} | Leurgans, Sue E.^{a; b} | Foroud, Tatiana M.ⁱ | Sweet, Robert A.^j | Graff-Radford, Neill^k | Bird, Thomas D.^l | Mayeux, Richard^{d; e; f; g; h} | Bennett, David A.^{a; b} | for the National Institute on Aging Late-Onset Alzheimer's Disease Genetics Study

Affiliations: [a] Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA | [b] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA | [c] Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA | [d] Gertrude H. Sergievsky Center, School of Public Health, Columbia University, New York, NY, USA | [e] Taub Institute for Research on Alzheimer's Disease and Aging Brain, School of Public Health, Columbia University, New York, NY, USA | [f] Department of Neurology, School of Public Health, Columbia University, New York, NY, USA | [g] Department of Psychiatry, College of Physicians and Surgeons, School of Public Health, Columbia University, New York, NY, USA | [h] Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA | [i] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA | [j] Departments of Psychiatry and Neurology, University of Pittsburgh, Pittsburgh, PA, USA | [k] Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, FL, USA | [l] Departments of Medicine, Neurology, and Medical Genetics, University of Washington, Seattle, WA, USA

Correspondence: [*] Correspondence to: Robert S. Wilson, PhD, Rush Alzheimer's Disease Center, Rush University Medical Center, 600 South Paulina Ave, Suite 1038, Chicago, IL 60612, USA. E-mail: [email protected].

Abstract: The study aim was to estimate the genetic contribution to individual differences in different forms of memory in a large family-based group of older adults. As part of the Late Onset Alzheimer's Disease Family Study, 899 persons (277 with Alzheimer's disease, 622 unaffected) from 325 families completed a battery of memory tests from which previously established composite measures of episodic memory, semantic memory, and working memory were derived. Heritability in these measures was estimated using the maximum likelihood variance component method, controlling for age, gender, and education. In analyses of unaffected family members, the adjusted heritability estimates were 0.62 for episodic memory, 0.49 for semantic memory, and 0.72 for working memory, where a heritability estimate of 1 indicates that genetic factors explain all of the phenotypic variance and a heritability of 0 indicates that genetic factors explain none. Adjustment for APOE genotype had little effect on these estimates. When analyses included affected and unaffected family members, adjusted heritability estimates were lower (0.47 for episodic memory, 0.32 for semantic memory, 0.42 for working memory). Adjusting for APOE slightly reduced the estimate for episodic memory (0.40) but had no effect on the remaining estimates. The results indicate that memory functions are under strong genetic influence in older persons with and without AD, and are only partly attributable to APOE. This suggests that genetic analyses of memory endophenotypes may help to identify genetic variants associated with AD.

Keywords: Alzheimer's disease, apolipoprotein E, heritability, memory

DOI: 10.3233/JAD-2010-101515

Journal: Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 249-255, 2011