APOE allele frequencies in suspected non-amyloid pathophysiology (SNAP) and the prodromal stages of Alzheimer's Disease

• Published in: PloS one 2017-11, Vol.12 (11), p.e0188501-e0188501
• Main Authors: Hohman, Timothy J, Dumitrescu, Logan, Oksol, Amy, Wagener, Madison, Gifford, Katherine A, Jefferson, Angela L
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloidosis; Apolipoproteins; Apolipoproteins E - genetics; Biology and Life Sciences; Biomarkers - metabolism; Brain - diagnostic imaging; Brain - metabolism; Female; Gene Frequency; Humans; Magnetic Resonance Imaging; Male; Medicine and Health Sciences; Neuroimaging; Pathological physiology; Prodromal Symptoms; Research and Analysis Methods
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0188501

Biomarker definitions for preclinical Alzheimer's disease (AD) have identified individuals with neurodegeneration (ND+) without β-amyloidosis (Aβ-) and labeled them with suspected non-AD pathophysiology (SNAP). We evaluated Apolipoprotein E (APOE) ε2 and ε4 allele frequencies across biomarker definitions-Aβ-/ND- (n = 268), Aβ+/ND- (n = 236), Aβ-/ND+ or SNAP (n = 78), Aβ+/ND+ (n = 204)-hypothesizing that SNAP would have an APOE profile comparable to Aβ-/ND-. Using AD Neuroimaging Initiative data (n = 786, 72±7 years, 48% female), amyloid status (Aβ+ or Aβ-) was defined by cerebrospinal fluid (CSF) Aβ-42 levels, and neurodegeneration status (ND+ or ND-) was defined by hippocampal volume from MRI. Binary logistic regression related biomarker status to APOE ε2 and ε4 allele carrier status, adjusting for age, sex, education, and cognitive diagnosis. Compared to the biomarker negative (Aβ-/ND-) participants, higher proportions of ε4 and lower proportions of ε2 carriers were observed among Aβ+/ND- (ε4: OR = 6.23, p0.15), but did show an association with SNAP defined using CSF tau (β = 0.004, p = 0.02). Thus, in a population with low levels of cerebrovascular disease and a lower prevalence of SNAP than the general population, APOE and known genetic drivers of AD do not appear to contribute to the neurodegeneration observed in SNAP. Additional work in population based samples is needed to better elucidate the genetic contributors to various etiological drivers of SNAP.