AV1451 TAU TRACER UPTAKE CORRELATES WITH HIPPOCAMPAL CA1 SUBFIELD ATROPHY IN AMYLOID-NEGATIVE INDIVIDUALS

Abstract

We present novel preliminary data demonstrating relationships between the amount of tau binding measured by AV1451 PET imaging and atrophy within hippocampal subfields measured by hippocampus-focused high-resolution structural MRI in individuals classified as either Amyloid-β positive or negative based on Florbetapir-PET imaging. While the cornu ammonis 1 (CA1) subfield is known to be an early site of tau pathology in Alzheimer's disease (AD) and Primary Age Related Tauopathy (PART, defined by the presence of tau-based neurofibrillary tangles in the absence of amyloid), it is unclear how tau pathology in PART relates to subfield structure. The dataset included 80 participants (27 Aβ positive: 9 controls, 13 Mild Cognitive Impairment (MCI), 5 AD; 53 Aβ negative: 37 controls, 14 MCI, 2 AD) in the ADNI study. Normalized tau tracer uptake in the medial temporal lobe (MTL) was measured from AV1451 PET within a composite cortical ROI consisting of Brodmann area 35 (BA35) region of perirhinal cortex and entorhinal cortex. Hippocampus wasn't included to avoid a known confound of high choroid plexus uptake. Hippocampal subfield volumes (CA1, CA4 and dentate gyrus (DG), subiculum (SUB)) were measured from high-resolution T2-weighted structural MRI using a joint label fusion technique implemented in the ASHS software. Both PET and atrophy measures were averaged across the hemispheres. We correlated a summary measure of MTL tau tracer uptake with hippocampal subfield volumes, with age and intracranial volume as covariates. In the Aβ positive group, CA1 had the strongest correlation with tracer uptake, followed by CA4DG, and SUB being marginally significant. In the Aβ negative group, all three subfields had significant correlation with tracer uptake, with CA1 marginally stronger than SUB (Figures 1 and 2, note different axes limits; Table 1). Amyloid positive. Amyloid negative. This is the first report relating AV1451 to high-resolution MRI specifically targeted for hippocampal subfield morphometry. The strong relationship between AV1451 tau uptake and CA1 atrophy in Aβ negative individuals suggests that AV1451 PET may be sensitive to the tau pathology of PART, which, in turn, drives MTL neurodegeneration and perhaps the cognitive symptoms of those in this group with MCI/AD designations.