Hippocampal subfield deformation shows unique patterns associated with amyloid‐beta, TDP‐43, and PHF‐tau burden

• DOI: 10.1002/alz.039864
• Publication Date: 2020-12-07T21:59:43Z
• Authors: Ashley Heywood; Julie A Schneider; David A Bennett; Konstantinos Arfa...; Faisal Beg; Lei Wang
• Keywords: Subiculum; Neuropathology

Abstract Background Alzheimer's dementia (AD) is the most common form of in adults over age 65, however, current diagnostic tools need to be improved. The relationships between clinical syndromes and pathological causes are complex, which makes accurate diagnosis difficult. goals develop an vivo hippocampal surface atlas from structural MRI that predictive postmortem β‐amyloid, paired helical filament (PHF‐tau) neurofibrillary tangles (NFTs) transactive response DNA‐binding protein‐43 (TDP‐43) neuropathologies. Method Using a sample 101 older two longitudinal cohort studies conducted by Rush Alzheimer’s Disease Center, we utilized shape analysis ante‐mortem T1‐weighted sMRI generate surfaces for whole hippocampus zones approximating underlying subfields using previously developed automated image‐segmentation pipeline (Freesurfer‐Initiated Large Deformation Diffeomorphic Metric Mapping; FSLDDMM). Multivariate linear regression models were constructed examine relationship pathology measures while accounting covariates include co‐existing pathologies other neuropathological variables (hippocampal sclerosis, Lewy bodies, gross infarcts, atherosclerosis, arteriosclerosis, cerebral amyloid angiopathy). These mapped onto locations. In previous 42 subjects same cohort, univariate not able examined due low power. Result A significant unique pattern deformation each neuropathology when seen. Specifically, β‐amyloid was associated with inward subiculum, where PHF‐tau NFTs along left tail within subiculum. TDP‐43 inclusions body CA1/subiculum border. Results corrected multiple comparisons random field theory (RFT) family‐wise error rate (FWER) < 0.05. Conclusion results indicate individual neuropathology, after covariates. With presented increased size, signature arose. may used represent biomarker post mortem disease could allow early aid selection trials.