P1‐008: SEX‐SPECIFIC ASSOCIATIONS OF CEREBROSPINAL FLUID TAU AND NEUROGRANIN CONCENTRATIONS WITH ALZHEIMER'S NEUROIMAGING SIGNATURES

• DOI: 10.1016/j.jalz.2019.06.033
• Publication Date: 2019-10-18T10:41:26Z
• Authors: Elizabeth E. Moore; Hailey A. Kresge; Omair A. Khan; Corey W. Bown; Dandan Liu; Kimberly R. Pechman; Lealani Mae Y. Ac...; Susan P. Bell; Niranjana Shashik...; Humza A. Ahmed; Maxim Turchan; Bennett A. Landman; Kaj Blennow; Henrik Zetterberg; Timothy J. Hohman; Angela L. Jefferson; Katherine A. Gifford
• Keywords: Neurogranin; Neuropathology

Prior work has identified an “Alzheimer's disease (AD) imaging signature” reflecting brain regions most vulnerable to AD-specific neurodegeneration that differentiates individuals with normal cognition from clinical AD. The neuropathology associated the regionally specific atrophy remains unclear. This study relates cerebrospinal fluid (CSF) biomarkers of AD (amyloid-beta (Aβ42), hyperphosphorylated tau (p-tau)); (total (t-tau)); axonal injury (neurofilament light (NFL)); and synaptic dysfunction (neurogranin) two available signatures. Vanderbilt Memory & Aging Project participants free dementia or stroke (n=153, 72±7 years) underwent fasting lumbar puncture multimodal 3T magnetic resonance imaging. T1-weighted images were post-processed using FreeSurfer. signatures calculated published guidelines (McEvoy et al., 2009; Schwarz 2016). Ordinary least square regressions related each CSF biomarker neuroimaging signature, adjusting for age, sex, race/ethnicity, education, diagnosis, apolipoprotein E ε4 status, in McEvoy signature models, intracranial volume. Secondary models tested a x sex interaction term on signature. Bootstrapped analyses partial correlations if pattern was more strongly one versus other. Increased t-tau (b=-1.3x10-4, p=0.005) NFL (b=-6.1x10-5, p=0.001) smaller P-tau (p=0.05) neurogranin (p=0.04) interacted associations driven by females (p-values<0.06). p-tau (b=-1.5x10-2, p=0.04), (b=-2.5x10-3, p=0.003), (b=-1.3x10-3, p=0.0001) Neurogranin present (p=0.04). Aβ42, t-tau, did not interact either statistically comparable relation Among older adults, increased evidence neurodegeneration, including axonopathy hyperphosphorylation, relate greater AD-affected regions. association between hyperphosphorylation dysfunction, appears females. These results suggest neuronal may be prominent women. Funding: Alzheimer's Association IIRG-08-88733, R01-AG034962, R01-AG056534, K24-AG046373, K23-AG045966, T32-GM007347.