P1‐271: CSF GLUCOSE TRACKS BRAAK STAGE TAU DEPOSITION

Abstract

Type 2 diabetes is a known risk factor for Alzheimer's disease (AD). Tau hyperphosphorylation, a marker of neurodegeneration, occurs in the brain of both type 2 diabetes and AD patients. Furthermore, CSF glucose is strongly associated with CSF total tau protein levels in AD patients. It is not known if CSF glucose is associated with regional tau deposition, however, and if such associations regionally vary depending on AD genetic risk factors, baseline diagnosis, or sex. Data from 142 aged adults was downloaded from the Alzheimer's Disease Neuroimaging Initiative (ADNI). CSF glucose levels were derived from standard lab assays. Fully preprocessed F18-AV-1451 positron emission tomography scans where coregistered to the subject's T1-weighted image in native space. Mean regional uptake in FreeSurfer defined regions was divided by mean uptake in the inferior cerebellum reference region to derive Standardized Uptake Value Ratios (SUVRs). Multiple linear regression regressed CSF glucose against regional AV-1451 SUVR in regions of interest. Due to the large number of cognitive normal subjects scanned (n=103), analyses were restricted to Braak stages 1/2 and 3/4. Interactions between CSF glucose and gender, family history of AD, and beta-amyloid (Aβ) status were also explored. Higher CSF glucose was significantly associated with lower tau deposition in the caudal anterior cingulate gyrus (Braak 4). Moderation analyses showed that only Mild Cognitive Impairment (MCI) and AD participants drove this association. A gender x CSF glucose interaction showed that higher CSF glucose was related to lower hippocampal tau deposition (Braak 2) in women but not men. Finally, for subjects with AD parental history, higher CSF glucose was linked to less regional tau deposition in all Braak stage 3 and 4 regions, particularly the lingual gyrus, fusiform gyrus, and isthmus of cingulate gyrus. Taken together, these results suggest that higher CSF glucose levels may be protective against early tau deposition among women, as well as later tau deposition among subjects with cognitive impairment or a parental history of AD. Future work will examine similar associations with peripheral insulin resistance and moderation by regional amyloid deposition.