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

Brian A Gordon, Austin McCullough, Shruti Mishra, Tyler M Blazey, Yi Su, John Christensen, Aylin Dincer, Kelley Jackson, Russ C Hornbeck, John C Morris, Beau M Ances, Tammie L S Benzinger, Brian A Gordon, Austin McCullough, Shruti Mishra, Tyler M Blazey, Yi Su, John Christensen, Aylin Dincer, Kelley Jackson, Russ C Hornbeck, John C Morris, Beau M Ances, Tammie L S Benzinger

Abstract

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.

Keywords: Amyloid; Atrophy; MRI; PET; Positron emission tomography; Tau; Thickness.

Figures

Fig. 1
Fig. 1
The relationship between global AD pathology and gray matter. Three GLMs were implemented to estimate vertex-wise relationships between (A) global tau PET summary measure, (B) Aβ mean cortical SUVR, or (C) global tau controlling for Aβ, and left-hemisphere cross-sectional cortical thickness. Spatiotemporal LMEs models were used to investigate relationships between (D) global tau and time from initial MRI, (E) global Aβ and time, or (F) global tau and time controlling for Aβ and time, and antecedent longitudinal change in cortical thickness. All models controlled for the main effects of gender, current age, and scan resolution. Cross-sectional models used the Qdec multiple comparisons correction (FDR) procedure at P < .025 level to approximate comparisons in both hemispheres. Longitudinal models used the LME FDR2 comparisons correction in MATLAB and accounted for comparisons in both hemispheres. Values depicted from each model are thresholded at the level of significance identified by their respective FDR procedures. Abbreviations: Aβ, amyloid β; AD, Alzheimer's disease; FDR, false discovery rate; GLM, general linear model; LMEs, linear mixed-effects; MRI, magnetic resonance imaging; PET, positron emission tomography; SUVR, standardized uptake value ratio.
Fig. 2
Fig. 2
The relationship between local AD pathology and gray matter. Linear mixed-effects models were implemented to model region-wise relationships between (A) local tau and time, (B) local Aβ and time, or (C) local tau and time controlling for local Aβ and time, on longitudinal local cortical thickness in all 34 FreeSurfer cortical regions. All models controlled for the main effects of gender, age, and scan resolution. Both hemispheres' values were averaged together. Values depicted are adjusted −log10(P) values after FDR correction for multiple comparisons. Abbreviations: AD, Alzheimer's disease; FDR, false discovery rate.

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