Abstract 150: Regional Molecular Alterations in Cerebral Amyloid Angiopathy-Related Hemorrhagic Lesions

Abstract

Background: Previous case reports suggested co-localization of tau but not β-Amyloid with cortical superficial siderosis (cSS) in cerebral amyloid angiopathy (CAA). We thus hypothesized that the tau load represents a continuum with amyloid accumulation in the disease cascade and that the tau load would be higher in lobes with cSS and intracerebral hemorrhages (ICH) when compared to the contralateral lobes without hemorrhages in CAA patients. Methods: The study included 26 cognitively healthy probable CAA patients (mean age 71±7.5, 53.8% male) who underwent multimodal MRI, Pittsburgh compound B (PiB, for amyloid), and 18 F-flortaucipir (FTP, for tau) PET imaging. Mean global cortical PiB uptake and FTP uptake were calculated in each lobar region. The presence of ICH and cSS were identified in each lobar region independent of molecular imaging. A pairwise comparison of PiB and FTP uptake was done between lobes with any hemorrhagic lesion (ICH/cSS) and their corresponding lobes without hemorrhages. Results: The FTP uptake was significantly higher in 8 frontal, 16 temporal, and 11 occipital lobes with hemorrhages compared to their corresponding contralateral lobes without hemorrhages (1.18±0.1 vs. 1.13±0.1; p=0.002, 1.28±0.1 vs. 1.20±0.1; p=0.004, 1.29±0.1 vs. 1.10±0.1; p=0.002, respectively) but not in parietal lobes (p=0.107). The PiB uptake was significantly higher in occipital lobes with hemorrhages compared to their contralateral lobes without hemorrhages (1.41±0.3 vs. 1.35±0.3, p=0.004) but there was no difference in the comparison of amyloid burden for the remaining lobar regions with or without hemorrhage (p>0.2 for all comparisons). Conclusions: Reduced PiB uptake at sites of larger hemorrhagic lesions (cSS/ICH) has been observed in the past so the lack of differences in amyloid between most lobes with and without hemorrhage was not surprising in our study. Our results otherwise show significantly increased tau load at most brain lobes with hemorrhagic lesions among CAA patients. Potential clinical effects of the tau burden related to cSS/ICH should be studied in larger CAA cohorts using appropriate clinical testing.