Excessive tau accumulation in the parieto-occipital cortex characterizes early-onset Alzheimer's disease

Abstract

Background: Early-onset Alzheimer’s disease (EOAD) is associated with a greater impairment of various non-memory functions, more rapid progression, and greater cortical hypometabolism and atrophy when compared to late-onset AD (LOAD) even when similar amyloid-β burden was present in positron emission tomography (PET) studies. We sought to investigate the differences in topographical patterns of tau accumulation between the early- and late-onset patients with AD and mild cognitive impairment (MCI). Methods: In 90 amnestic MCI and mild to moderate AD patients who completed 18F-AV-1451 and 18F-florbetaben positron emission tomography scans, 59 amyloid-positive patients were included (11 EOAD, 10 EOMCI, 21 LOAD, and 17 LOMCI). We compared cortical 18F-AV-1451 and 18F-florbetaben binding between each patient group and corresponding amyloid-negative age-matched controls. Results: Compared to each control group, both EOAD and LOAD groups showed markedly increased 18F-AV- 1451 binding across the entire neocortex, while only the LOMCI group showed increased binding in the medial temporal cortex. In contrast to no difference in cortical 18F-AV-1451 binding between the EOMCI and LOMCI, the EOAD showed greater 18F-AV-1451 binding in the parieto-occipital cortex than LOAD. The parieto-occipital 18F-AV-1451 binding correlated with the visuospatial dysfunction in EOAD spectrum, while the binding in the temporal cortex correlated with verbal memory dysfunction in LOAD spectrum. Cortical 18F-florbetaben binding did not differ between the EOAD and LOAD groups. Conclusion: EOAD patients have a greater tau burden, particularly in the parieto-occipital cortex than LOAD patients. Distinct topographic distribution of tau may influence the nature of cognitive impairment in EOAD patients.