title: Interaction Between Midlife Blood Glucose and APOE Genotype Predicts Later Alzheimer's Disease Pathology.
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.
authors.affiliation: Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Bangen
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|The Framingham Heart Study, Framingham, MA, USA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|The Framingham Heart Study, Framingham, MA, USA.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.affiliation: Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.affiliation: The Framingham Heart Study, Framingham, MA, USA.|Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|The Framingham Heart Study, Framingham, MA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|The Framingham Heart Study, Framingham, MA, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|The Framingham Heart Study, Framingham, MA, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|The Framingham Heart Study, Framingham, MA, USA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.affiliation: Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001786:Blood Glucose; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012307:Risk Factors; D014652:Vascular Diseases / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D001786:Blood Glucose
keywords: Alzheimer’s disease; apolipoprotein E (APOE); diabetes; glucose; neuropathology; vascular risk