Vascular Risk and β-Amyloid Are Synergistically Associated with Cortical Tau

Jennifer S. Rabin, Hyun Sik Yang, Aaron P. Schultz, Bernard J. Hanseeuw, Trey Hedden, Anand Viswanathan, Jennifer R. Gatchel, Gad A. Marshall, Emily Kilpatrick, Hannah Klein, Vaishnavi Rao, Rachel F. Buckley, Wai Ying Wendy Yau, Dylan R. Kirn, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, Jasmeer P. Chhatwal

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Objective: Neuropathological studies have demonstrated that cerebrovascular disease and Alzheimer disease (AD) pathology frequently co-occur in older adults. The extent to which cerebrovascular disease influences the progression of AD pathology remains unclear. Leveraging newly available positron emission tomography (PET) imaging, we examined whether a well-validated measure of systemic vascular risk and β-amyloid (Aβ) burden have an interactive association with regional tau burden. Methods: Vascular risk was quantified at baseline in 152 clinically normal older adults (mean age = 73.5 ± 6.1 years) with the office-based Framingham Heart Study cardiovascular disease risk algorithm (FHS-CVD). We acquired Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET imaging on the same participants. Aβ PET was performed at baseline; tau PET was acquired on average 2.98 ± 1.1 years later. Tau was measured in the entorhinal cortex (EC), an early site of tau deposition, and in the inferior temporal cortex (ITC), an early site of neocortical tau accumulation associated with AD. Linear regression models examined FHS-CVD and Aβ as interactive predictors of tau deposition, adjusting for age, sex, APOE ε4 status, and the time interval between baseline and the tau PET scan. Results: We observed a significant interaction between FHS-CVD and Aβ burden on subsequently measured ITC tau (p < 0.001), whereby combined higher FHS-CVD and elevated Aβ burden was associated with increased tau. The interaction was not significant for EC tau (p = 0.16). Interpretation: Elevated vascular risk may influence tau burden when coupled with high Aβ burden. These results suggest a potential link between vascular risk and tau pathology in preclinical AD. Ann Neurol 2019; 1–8 ANN NEUROL 2019;85:272–279.

Original languageEnglish
Pages (from-to)272-279
Number of pages8
JournalAnnals of Neurology
Volume85
Issue number2
DOIs
StatePublished - Feb 2019
Externally publishedYes

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