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The DRD2 Taq1A A1 Allele May Magnify the Risk of Alzheimer’s in Aging African-Americans

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Abstract

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys cognitive skills and the ability to perform the simplest tasks. More than 5 million Americans are afflicted with Alzheimer’s; a disorder which ranks third, just behind heart disease and cancer, as a cause of death for older people. With no real cure and in spite of enormous efforts worldwide, the disease remains a mystery in terms of treatment. Importantly, African-Americans are two times as likely as Whites to develop late-onset Alzheimer’s disease and less likely to receive timely diagnosis and treatment. Dopamine function is linked to normal cognition and memory and carriers of the DRD2 Taq1A A1 allele have significant loss of D2 receptor density in the brain. Recent research has shown that A1 carriers have worse memory performance during long-term memory (LTM) updating, compared to non-carriers or A2-carriers. A1carriers also show less blood oxygen level-dependent (BOLD) activation in the left caudate nucleus which is important for LTM updating. This latter effect was only seen in older adults, suggesting magnification of genetic effects on brain functioning in the elderly. Moreover, the frequency of the A1 allele is 0.40 in African-Americans, with an approximate prevalence of the DRD2 A1 allele in 50% of an African-American subset of individuals. This is higher than what is found in a non-screened American population (≤ 28%) for reward deficiency syndrome (RDS) behaviors. Based on DRD2 known genetic polymorphisms, we hypothesize that the DRD2 Taq1A A1 allele magnifies the risk of Alzheimer’s in aging African-Americans. Research linking this high risk for Alzheimer’s in the African-American population, with DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM, could pave the way for novel, targeted pro-dopamine homeostatic treatment.

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Acknowledgments

Dr. Kenneth Blum is the owner of US and foreign patents related to genetic testing. Dr. Rajendra D. Badgaiyan is supported by the National Institutes of Health (NIH) grants R01NS073884 and 1R21MH073624, and Dr. Marjorie C. Gondré-Lewis is supported by NIH/NIAAA grants R01AA021262, NIH/NIMHD grant R41MD12318 (to MGL and KB) and G12MD007597.

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Authors and Affiliations

  1. Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA

    Kenneth Blum

  2. Department of Psychiatry and Behavioral Sciences, Keck Medicine University of Southern California, Los Angeles, CA, USA

    Kenneth Blum & David Baron

  3. Division of Applied Clinical Research & Education, Dominion Diagnostics, LLC, North Kingstown, RI, USA

    Kenneth Blum

  4. Department of Neurogenetics, Igene, LLC, Austin, TX, USA

    Kenneth Blum

  5. Division of Reward Deficiency Syndrome and Addiction Therapy, Nupathways, Inc., Innsbrook, MO, USA

    Kenneth Blum

  6. Department of Clinical Neurology, Path Foundation, New York, NY, USA

    Kenneth Blum

  7. Division of Neuroscience Based Addiction Therapy, The Shores Treatment & Recovery Center, Port Saint Lucie, FL, USA

    Kenneth Blum

  8. Eötvös Loránd University, Institute of Psychology, Budapest, Hungary

    Kenneth Blum

  9. Department of Psychiatry and Behavioral Health, Richmond University Medical Center, 355 Bard Avenue, Staten Island, NY, 10310, USA

    Kenneth Blum & Rajendra D. Badgaiyan

  10. NeuroPsychoSocial Genomics Core, National Human Genome Center, Howard University, Washington, DC, USA

    Kenneth Blum, Georgia M. Dunston & Marjorie C. Gondré-Lewis

  11. Department of Psychology, Curry College, Milton, MA, USA

    Edward J. Modestino & Bruce Steinberg

  12. Center for Psychiatric Medicine, North Andover, MA, USA

    Thomas McLaughlin

  13. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA

    Mark S. Gold

  14. Developmental Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC, USA

    Marjorie C. Gondré-Lewis

  15. Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC, USA

    Marjorie C. Gondré-Lewis

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  1. Kenneth Blum
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Blum, K., Badgaiyan, R.D., Dunston, G.M. et al. The DRD2 Taq1A A1 Allele May Magnify the Risk of Alzheimer’s in Aging African-Americans. Mol Neurobiol 55, 5526–5536 (2018). https://doi.org/10.1007/s12035-017-0758-1

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