Tau spreading facilitated by distinct regional amyloid patterns in aging and Alzheimer’s disease

Ziel/Aim To assess the contribution of regional amyloid load to tau spreading in a cohort of amyloid-positive (Aß+) subjects using PET data.

Methodik/Methods Data of 41 cognitively unimpaired (CU) and 31 MCI patients was retrieved from ADNI, who had undergone two ¹⁸F-AV1451 (tau) and a baseline ¹⁸F-AV45 (amyloid) PET scan. Pre-processed PET scans were z-transformed using Aß- and age-matched CU subjects (n=38) as reference group. Subsequently, tau PET z-maps were thresholded at z>1.96 and annual tau z-score change maps were computed. To identify linked regional combinations of baseline amyloid distribution and tau spreading, baseline amyloid z-maps and annual tau change maps were submitted to a data-driven parallel ICA which yields maximally correlated component pairs of these two measures. Next, regional overlap between resulting component pairs was quantified using the dice similarity coefficient (DSC). Finally, group-specific spearman correlations were performed to test the association between baseline amyloid load and annual tau change extracted from the component pairs.

Ergebnisse/Results The p-ICA resulted in three significant component pairs with relative spatial overlap suggesting a spatial disconnect between antecedent amyloid burden and subsequent tau spreading. Greater amyloid burden was positively associated with higher annual tau change in component pairs 1 and 3 in the CU group, and in component pair 2 for the MCI group pointing towards a stage-dependent role of regional amyloid on tau spreading.

Schlussfolgerungen/Conclusions Baseline amyloid-distribution patterns may inform on subsequent regional increases of tau pathology, and thus the neuropathological course of Alzheimer’s disease.