The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable.
Late-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.
Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Jesse
J
Mez
Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
Shubhabrata
S
Mukherjee
Department of Biostatistics, University of Washington, Seattle, WA, USA.
Timothy
T
Thornton
Department of Biostatistics, University of Kentucky College of Public Health, Lexington, KY, USA.
David W
DW
Fardo
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Emily
E
Trittschuh
G2P Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Sheila
S
Sutti
Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Richard
R
Sherva
Department of Biology, Brigham Young University, Provo, UT, USA.
John S
JS
Kauwe
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adam C
AC
Naj
Miller School of Medicine, Hussman Institute for Human Genomics and Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami, Miami, FL, USA.
Gary W
GW
Beecham
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Alden
A
Gross
IU Health Neuroscience Center, Department of Radiology, Indiana University, Indianapolis, IN, USA.
Andrew J
AJ
Saykin
G2P Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Robert C
RC
Green
Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: pcrane@uw.edu.
Paul K
PK
Crane
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology*; D002875:Chromosomes / Q000235:genetics; D030541:Databases, Genetic; D056344:Executive Function; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008568:Memory; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
Atypical Alzheimer's disease; Dysexecutive Alzheimer's disease; Executive function; Genetics; Heritability; Memory