Grant: Travel Awards - Institute Community Support

Aims Hippocampal atrophy is a hallmark of AD and is often associated with tau and amyloid-B pathology in cross-sectional studies. The objective of this study was to verify if these associations were more specific to hippocampal tau pathology in a longitudinal design. Methods 185 subjects (mean age: 70.1) underwent structural MRI, Tau-PET using [18F]MK6240 and Amyloid-PET using [18F]AZD4694. Of those subjects, 101 had a follow-up interval averaging 2.09 years. Using MAGeT-Brain, we segmented lateralized hippocampi into 1) dentate gyrus and CA4 (DG/CA4), 2) CA2 and CA3 (CA2/CA3), 3) CA1, 4) strata radiatum, lacunosum and moleculare (SRLM), and 5) subiculum. We associated hippocampal subfield volumes and volume changes with Braak 2 tau, Braak 3 tau, and global amyloid-B positivity, SUVR and SUVR changes. Braak 2 tau and global amyloid were also used to define amyloid and tau positivity. Statistical models were corrected for age, education, ApoE4, sex, follow-up interval and intracranial volume. Results We found significant negative associations between cross-sectional DG/CA4, subiculum and SRLM volumes and Braak 2, Braak 3 and global amyloid-B SUVR. The same regions were also significantly smaller in Tau positive and in amyloid-B positive subjects. However, only Braak 2 SUVR change was significantly associated with hippocampal volume changes in bilateral CA1, right subiculum and SRLM as well as left DG/CA4. Conclusions While all AD-associated measures were associated with hippocampal subfield atrophy, hippocampal tau signal increases was also significantly correlated with subfield atrophy. This offers evidence that as tau neuropathology progresses outside of the medial temporal lobe, hippocampal tau accumulation is still the most determining event underlying hippocampal atrophy.