Post by Deborah Joye

What's the science?

Alzheimer’s disease is hallmarked by the accumulation of both beta-amyloid (Aβ) protein aggregates between nerve cells and tau protein ‘tangles’ that build up inside of cells. Build-up of Aβ and tau ultimately results in cell death. By the time a diagnosis occurs, build-up of tau and Aβ has usually progressed past the state where intervention is possible. Recently, there has been an increasing effort to identify preclinical risk factors that may aid in preventative measures against Alzheimer’s disease. Studies have shown that cerebrovascular disease (affecting blood flow to the brain) and Alzheimer’s disease pathology often co-occur in older adults, however it’s not clear how cerebrovascular disease might contribute to the progression of Alzheimer’s pathology. This week in Annals of Neurology, Rabin and colleagues use positron emission tomography (PET) imaging to demonstrate that increases in vascular disease may interact with Aβ build-up to increase accumulation of tau tangles.

How did they do it?

The authors measured vascular risk in 152 clinically normal older adults (mean age = 73.5 ± 6.1 years) using the well-validated Framingham Heart Study cardiovascular disease risk algorithm (which measures risk using relevant factors such as age, weight, and blood pressure). The authors then performed PET imaging on the same individuals using specific tracers that bind to Aβ (11C Pittsburgh compound B) and tau (18F-flortaucipir). Since tau can build up in individuals that do not develop Alzheimer’s disease, tau accumulation was measured in two places: the entorhinal cortex, a common site of early tau deposition in aging populations, and the inferior temporal cortex, an early site of tau accumulation associated with Alzheimer’s disease. The authors then used linear regression models (statistical model that investigates the relationship between two variables) to examine vascular risk and Aβ as interactive predictors of tau deposition, controlling for individual variables such as age and sex.

What did they find?

The authors’ analysis revealed an interaction between vascular risk and Aβ build-up that was associated with tau accumulation in the inferior temporal cortex, a region where tau accumulation occurs early on the the progression of Alzheimer’s disease. Specifically, when vascular risk was higher and Aβ build-up was higher, there was an increase in tau buildup. Interestingly, vascular risk and Aβ build-up were not associated with increased tau accumulation in the entorhinal cortex, suggesting that vascular risk may interact with Aβ specifically in the pre-clinical stages of Alzheimer’s disease.