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Aortic Stiffness Linked to Greater Rhinal and Entorhinal Tau Burden, Suggesting Possible Therapeutic Target

Higher aortic stiffness was associated with greater rhinal and entorhinal tau burden in a cross-sectional analysis of Framingham Heart Study data, according to a paper published online June 6 in the New England Journal of Medicine.

“Findings suggest that aortic stiffness, which is potentially modifiable, may be a probable independent target for prevention of tau-related pathologies," concluded Leroy L. Cooper, PhD, MPH, assistant professor of biology at Vassar College, and colleagues.

Intrigued by previous studies suggesting that excessive pressure and flow pulsatility may contribute to impaired clearance of beta amyloid and tau protein from the brain, Dr. Cooper and colleagues hypothesized that measures of aortic stiffness and pressure pulsatility might be associated with beta amyloid plaques and tau burden among individuals without dementia.

They analyzed data from the Framingham Heart Study Third Generation Cohort's third examination. The group of 3,171 individuals included 3,092 who successfully underwent comprehensive hemodynamic evaluations. A subset of 270 participants without dementia underwent a positron emission tomography (PET); 13 were excluded due to missing covariate data.

The final sample of 257 participants all had three measures of aortic stiffness and pressure pulsatility, including carotid-femoral pulse wave velocity, central pulse pressure (CPP), and forward wave amplitude (FWA). These measures were analyzed for any association with global beta amyloid plaques and regional tau were assessed using PET tracers.

Participants were all White with western European ancestry. Women accounted for 49 percent of the cohort.

Dr. Cooper and colleagues used multivariable models to find that higher CPP (p =.045) and FWA (p= .04) were associated with greater entorhinal tau burden. Likewise, higher CPP (p= 03) and FWA (p= .03) were associated with greater rhinal tau burden.

Those associations were most prominent in participants over the age of 60. Higher levels of all aortic stiffness and pressure pulsatility measures (p =.001 and .02, respectively) were linked to higher entorhinal tau burden among older but not younger participants.
No associations were seen between measures of aortic stiffness and the level of global beta amyloid plaques or tau burden in the amygdala, inferior temporal or precuneus.

“Our data reveal that abnormal central vascular hemodynamics are associated with higher regional tau burden in brain regions that are vulnerable to early tau protein deposition, independent of brain amyloidosis," Dr. Cooper and colleagues concluded.

The mechanism of the association, they hypothesized, may be due to elevated cerebrovascular resistance and chronic hypoperfusion of gray matter in vulnerable brain regions. But they noted: “Additional studies that address the hypoperfusion hypothesis are needed."

Among the study's limitations, they noted, are its cross-sectional design, its all-White population, and their relatively young age.

Dr. Cooper had no conflicts to disclose.

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Cooper LL, O'Donnell A, Beiser AS, et al. Association of aortic stiffness and pressure pulsatility with global amyloid-β and regional tau burden among Framingham Heart Study participants without dementia. JAMA Neurol 2022; Epub June 6.​