Spatially distinct atrophy is linked to β-amyloid and tau in preclinical Alzheimer disease

Objectives: To determine whether an MRI-based Alzheimer disease (AD) signature biomarker can detect tau-related neurodegeneration in preclinical AD, and to assess whether AD signature cortical thinning is associated with cognitive changes in cognitively normal (CN) older individuals. Methods: In a large cohort of CN individuals (n = 188), we measured the hippocampal volume and cortical thickness within independently defined AD signature regions. We cross-sectionally assessed the associations between AD signature cortical thinning or hippocampal atrophy with CSF biomarkers of tau (increased tau) and beta-amyloid (A beta) (decreased A beta 42). We also examined the impact of AD signature cortical thinning or other biomarker changes (i.e., hippo-campal atrophy, reduced CSF A beta 42, or increased CSF tau) on cognitive performance in CN individuals. Results: Elevated CSF tau was associated with AD signature cortical thinning but not hippocampal atrophy. In contrast, decreased CSF A beta 42 was associated with hippocampal loss but not AD signature cortical thinning. In addition, AD signature cortical thinning was associated with lower visuospatial performance. Reduced CSF A beta 42 was related to poorer performance on episodic memory. Conclusions: Spatially distinct neurodegeneration is associated with A beta and tau pathology in preclinical AD. A beta deposition and AD signature cortical atrophy independently affect cognition in CN older individuals.