Interaction Between Midlife Blood Glucose and APOE Genotype Predicts Later Alzheimer’s Disease Pathology

Article type: Research Article

Authors: Bangen, Katherine J.^{a; b; *} | Himali, Jayandra J.^{c; d} | Beiser, Alexa S.^{c; d; e} | Nation, Daniel A.^f | Libon, David J.^g | Fox, Caroline S.^{d; h} | Seshadri, Sudha^{c; d} | Wolf, Philip A.^{c; d} | McKee, Ann C.^{c; d} | Au, Rhoda^{c; d} | Delano-Wood, Lisa^{a; b}

Affiliations: [a] Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [b] Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA, USA | [c] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [d] The Framingham Heart Study, Framingham, MA, USA | [e] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [f] Department of Psychology, University of Southern California, Los Angeles, CA, USA | [g] Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA | [h] Division of Endocrinology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Katherine J. Bangen, PhD, 3350 La Jolla Village Drive, Mail Code 151B, San Diego, CA 92161, USA. Tel.: +1 858 552 8585 x5794; Fax: +1 858 642 6340; E-mail: [email protected].

Abstract: Elevated blood glucose and the apolipoprotein (APOE) ɛ4 allele have both been associated with increased dementia risk; however, the neuropathological mechanisms underlying these associations remain unclear. We examined the impact of APOE genotype and midlife blood glucose on post-mortem vascular and Alzheimer’s disease (AD) neuropathology. Ninety-four participants from the Framingham Heart Study without diagnosed diabetes underwent health examination at midlife and brain autopsy at death. Histopathological measures of vascular and AD neuropathology were obtained and analyzed. Results demonstrated that, among APOE ɛ4 carriers, elevated blood glucose was associated with more severe AD pathology. There was no such relationship with vascular pathology. In a relatively healthy sample with low vascular risk burden, midlife elevated blood glucose was associated with greater AD pathology among APOE ɛ4 carriers. A better understanding of interactive effects of APOE genotype and vascular risk on neuropathology has implications for identification of individuals at risk for decline and long-term preventive treatment.

Keywords: Alzheimer’s disease, apolipoprotein E (APOE), diabetes, glucose, neuropathology, vascular risk

DOI: 10.3233/JAD-160163

Journal: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1553-1562, 2016