Abstract 103: Cortical tau Pathology in Cerebral Amyloid Angiopathy

Abstract

Introduction: Cerebral amyloid angiopathy (CAA), a condition related to Alzheimer’s Disease, causes ischemic and hemorrhagic brain injury and contributes to cognitive impairment. Vascular amyloid, the hallmark of CAA, can be detected using amyloid PET imaging. We used selective tau imaging to understand the degree and associations of tau aggregation and deposition in patients with CAA. Methods: Thirty-four patients with probable CAA but without cognitive impairment were prospectively enrolled. Selective tau imaging was performed using PET tracer flortaucipir (FTP) and amyloid imaging was obtained with Pittsburgh Compound B PET. Global and region of interest based (ROI) standardized uptake value ratios (SUVR) were calculated from PET acquisitions. High resolution multimodal MRIs were obtained for each patient and markers of CAA-related structural injury were quantified. Results: The mean age ( + SD) of the patients was 69 + 6, 38% were female. Thirteen patients (38%) enrolled without intracerebral hemorrhage (ICH). Mean cortical FTP uptake was 1.18 + 0.11 (tau load, in SUVR). Five patients were tau positive based on FTP SUVR > 1.28 from a posterior cingulate cortex ROI, a previously validated method. Mean global cortical FTP uptake correlated with cortical amyloid load (r=0.37, p=0.04), centrum semiovale perivascular spaces (cs-PVS, r=0.49, p=0.004), extent of cortical superficial siderosis (cSS, r=0.44, p=0.01), and showed a trend for correlation with extent of leukoaraiosis (r=0.33, p=0.059). The associations with amyloid load and cs-PVS remained significant in multivariable models. Cortical FTP uptake was not associated with age, sex, vascular risk factors, presence of ICH or any of the CAA-related focal lesions (cerebral microbleeds, microinfarcts, lacunes), all p>0.2. Conclusions: Our results show that many patients with CAA have some degree of cortical tau deposition, but severe tau positivity was not frequent (15%) in this cognitively normal CAA cohort, considering that 30% of healthy older adults were positive in other studies. The associations of cortical tau with brain amyloid and CAA-specific markers of global brain injury suggest that vascular amyloid might trigger tau deposition which, in turn, might increase parenchymal damage.