SUBJECT-LEVEL ASSESSMENT OF REGIONAL CORRELATIONS BETWEEN TAU-PET, AMYLOID-PET, MRI AND FDG-PET ACROSS THE CLINICAL SPECTRUM OF ALZHEIMER’S DISEASE

Abstract

Neuroimaging modalities can measure different aspects of the disease process in Alzheimer's disease (AD), such as atrophy on MRI, as well as hypometabolism and the presence of tau and beta-amyloid proteins in the brain on PET, providing the opportunity to assess inter-relationships between these disease biomarkers. We aimed to assess subject-level correlations in the regional cortical distribution of tau-PET uptake, amyloid-PET uptake, MRI atrophy and [18F] fluorodeoxyglucose (FDG-PET) hypometabolism across the clinical spectrum of Alzheimer's disease (AD), including atypical and typical clinical presentations. Eighty-three amyloid-positive subjects with atypical (n=24) or typical (n=24 young-AD, n=35 old-AD) presentations of AD were identified that had undergone [18F]AV-1451 tau-PET, Pittsburgh Compound B (PiB) PET, FDG-PET and volumetric MRI. Regional measurements of the degree of grey matter atrophy, hypometabolism, tau and amyloid burden were calculated for 76 cortical regions using both a Z score and SUVR approach. Spearman correlations were performed between modalities for each subject for each approach, and the strength of the correlations were assessed across disease group. We observed some consistent trends in the data regardless of disease group or analysis approach. Both the regional distribution of FDG-PET hypometabolism and MRI atrophy correlated more strongly with regional tau-PET than amyloid-PET uptake, with greater tau-PET uptake observed in regions with reduced metabolism and volume. Furthermore, tau-PET uptake correlated more strongly with both FDG-PET and MRI compared with amyloid-PET. A similar degree of correlation was identified between MRI atrophy and both tau-PET uptake and FDG-PET hypometabolism; although these correlations tended to be lower in the old-AD group compared to the atypical AD and young-AD group. The regional distribution of tau deposition measured on PET correlates most closely with regional patterns of hypometabolism and atrophy in AD, with little relationship observed between these disease biomarkers and the distribution of beta-amyloid. These results shed light on the underlying relationships between proteins and neurodegeneration in AD.