SPATIAL CORRESPONDENCE OF ALZHEIMER’S DISEASE-RELATED TAU PATHOLOGY AND GREY MATTER ATROPHY DISTRIBUTION WITH INTRINSIC FUNCTIONAL BRAIN NETWORKS

Abstract

Neuropathological studies have shown that typical tau pathology in Alzheimer's disease (AD) preferentially affects specific brain regions whereas others remain relatively spared. The distinct regional spread of tau pathology in AD may be a consequence of the intrinsic network structure of the human brain and underlie regional grey matter (GM) atrophy. The spatially distributed brain regions that are most affected by the spread of tau pathology or atrophy may hence reflect an interconnected neuronal system. We characterized the distribution profiles of tau pathology and GM atrophy in AD using 18F-AV 1451 tau-sensitive positron emission tomography (PET) and structural magnetic resonance imaging (MRI), and studied these patterns in relation to the functional network organization of the human brain. We quantified the spatial correspondence of the regional distribution patterns of PET-evidenced tau pathology and regional GM atrophy with functional brain networks characterized by large-scale resting state functional magnetic resonance imaging (rs-fMRI) data in healthy subjects. Regional distribution patterns of increased PET-evidenced tau pathology or decreased GM intensity in AD compared to controls were characterized in two independent samples of prodromal and manifest AD cases (Swedish BioFINDER study, n=44; ADNI study, n=35). In the BioFINDER study we found that the tau pattern involved predominantly inferior, medial, and lateral temporal cortical areas, the precuneus, and lateral parietal and occipital cortex (Figure 1). This pattern overlapped primarily with the dorsal attention, and to some extent with higher visual, limbic, and parts of the default-mode network. PET-evidenced tau pathology in the ADNI replication sample, which represented a more prodromal group of AD cases, was less pronounced but showed a highly similar spatial distribution profile, suggesting an earlier-stage snapshot of a consistently progressing regional pattern. Preliminary analyses of atrophy patterns in the BioFINDER sample suggested an overlapping pattern with tau spread but with markedly less isocortical involvement.