• Jesse Mez, Shubhabrata Mukherjee, Timothy Thornton, David W Fardo, Emily Trittschuh, Sheila Sutti, Richard Sherva, John S Kauwe, Adam C Naj, Gary W Beecham, Alden Gross, Andrew J Saykin, Robert C Green, Paul K Crane, Executive Prominent Alzheimer's Disease: Genetics and Risk Factors (EPAD:GRF), Alzheimer's Disease Neuroimaging Initiative (ADNI1), and Alzheimer's Disease Genetics Consortium (ADGC).
• Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
• Neurobiol. Aging. 2016 May 1; 41: 115-121.

AbstractLate-onset Alzheimer's disease (LOAD) can present heterogeneously, with several subtypes recognized, including dysexecutive AD. One way to identify people with dysexecutive AD is to consider the difference between memory and executive functioning, which we refer to as the executive prominent/memory prominent spectrum. We aimed to determine if this spectrum was heritable. We used neuropsychological and genetic data from people with mild LOAD (Clinical Dementia Rating 0.5 or 1.0) from the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. We cocalibrated the neuropsychological data to obtain executive functioning and memory scores and used their difference as a continuous phenotype to calculate its heritability overall and by chromosome. Narrow-sense heritability of the difference between memory and executive functioning scores was 0.68 (standard error 0.12). Single nucleotide polymorphisms on chromosomes 1, 2, 4, 11, 12, and 18 explained the largest fraction of phenotypic variance, with signals from each chromosome accounting for 5%-7%. The chromosomal pattern of heritability differed substantially from that of LOAD itself. Copyright © 2016 Elsevier Inc. All rights reserved.

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