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

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 AE 6.1 years) with the office-based Framingham Heart Study cardiovascular disease risk algorithm (FHS-CVD). We acquired Aβ ( 11 C-Pittsburgh compound B) and tau ( 18 F-flortaucipir) PET imaging on the same participants. Aβ PET was performed at baseline; tau PET was acquired on average 2.98 AE 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.

Association of Apolipoprotein E ɛ4, Educational Level, and Sex With Tau Deposition and Tau-Mediated Metabolic Dysfunction in Older Adults

“…57 There is increasing evidence that vascular risk has weak to modest associations with tau deposition. In separate models, we did observe a modest accounting of variance by cerebrovascular disease risk on entorhinal cortex tau burden after accounting for the association of global amyloid burden, consistent with prior reports 33,58 that cerebrovascular disease and amyloid pathology can concurrently influence tau burden.…”

Differential protein expression in diverse brain areas of Parkinson’s and Alzheimer’s disease patients

“…Furthermore, VD brain blood barrier dysfunction and altered cerebrovascular permeability can result in overproduction of Aβ and oxidative stress 64 . Although elevated vascular risk may influence tau burden when coupled with high Aβ burden we do not see Aβ accumulation in VD patients 65 . Remarkably, we observed SNCA over-production in SNpc VD samples.…”

Reciprocal Predictive Relationships between Amyloid and Tau Biomarkers in Alzheimer's Disease Progression: An Empirical Model

“…In HC, lower CSF A␤42 variably predicted changes in cognitive status, so it might be speculated that identifying and targeting the mechanism(s) underlying this biomarker might prevent early changes in cognitive status due to AD in healthy elderly people. The prediction of A␤ deposition by CSF p-tau seen in HC might also suggest that strategies targeting tau, either directly or indirectly via other processes that lead to tau accrual (Kim et al, 2018;Rabin et al, 2019; e.g., cerebral small vessel disease, vascular risk factors, diabetes, head trauma, etc. ), might slow amyloid deposition in asymptomatic people.…”