Cross-sectional and longitudinal atrophy is preferentially associated with tau rather than amyloid β positron emission tomography pathology

Introduction: Structural magnetic resonance imaging is a marker of gray matter health and decline that is sensitive to impaired cognition and Alzheimer's disease pathology. Prior work has shown that both amyloid β (Aβ) and tau biomarkers are related to cortical thinning, but it is unclear what unique influences they have on the brain. Methods: Aβ pathology was measured with [¹⁸F] AV-45 (florbetapir) positron emission tomography (PET) and tau was assessed with [¹⁸F] AV-1451 (flortaucipir) PET in a population of 178 older adults, of which 123 had longitudinal magnetic resonance imaging assessments (average of 5.7 years) that preceded the PET acquisitions. Results: In cross-sectional analyses, greater tau PET pathology was associated with thinner cortices. When examined independently in longitudinal models, both Aβ and tau were associated with greater antecedent loss of gray matter. However, when examined in a combined model, levels of tau, but not Aβ, were still highly related to change in cortical thickness. Discussion: Measures of tau PET are strongly related to gray matter atrophy and likely mediate relationships between Aβ and gray matter.