Article

Increased Tau Burden Observed in Abnormal Central Vascular Hemodynamics

Author(s):

Patients who demonstrated increased central pulse pressure and forward wave amplitude had greater entorhinal tau burden. These measures were not associated with amygdala, inferior temporal, nor precuneus tau burden.

Leroy Cooper, PhD, MPH, assistant professor of biology, Vassar College

Leroy Cooper, PhD, MPH

Recently published cross-sectional data from the Framingham Heart Study (FHS) showed that higher aortic stiffness and pressure pulsatility were associated with greater rhinal and entorhinal tau burden, supporting the hypothesis that abnormal central vascular hemodynamics contributes to increased tau in specific brain regions susceptible to early tau protein deposition.1

"Aortic stiffness is potentially modifiable and, therefore, represents a probably independent target for prevention of tau-related pathologies," lead investigator Leroy Cooper, PhD, MPH, assistant professor of biology, Vassar College, and colleagues, concluded.

Published in JAMA Neurology, the study included 257 middle-aged and older adults without dementia who successfully underwent comprehensive hemodynamic evaluations and were considered on the spectrum of vascular risk. After undergoing PET scans, arterial tonometry was used to assess measures of aortic stiffness and pressure pulsatility, including carotid-femoral pulse wave velocity (CFPWV), central pulse pressure (CPP), and forward wave amplitude (FWA).

The study also used C-Pittsburgh compound B (PiB) and 18F-flortaucipir (FTP) to assess the burden of amyloid-ß (Aß) plaques and tau protein deposition in the brain, respectively. Participants in the highest Aß quintile (≥ 1.09 PiB distribution volume ration) were classified as positive for elevated Aß burden. FTP retention was assessed in the rhinal cortex using vertex-wise surface mapping of the cortical ribbon at the midpoint of the gray matter.

Findings on multivariable models showed that increased CPP (ß per standard deviation [SD], 0.17; SE, 0.09; 95% CI, 0.01-0.32; P = .03) were associated with greater entorhinal tau burden. In similar models, higher CPP (ß per SD, 0.19; SE, 0.09; 95% CI, 0.02-0.36; P = .03) and FWA (ß per SD, 0.17; SE, 0.08; 95% CI, 0.01-0.32; P = .03) were associated with greater rhinal tau burden. Measures of aortic stiffness and pressure pulsatility were not associated with amygdala, inferior temporal, and precuneus tau burden, nor were they associated with Aß burden.

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Older participants, aged 60 years and above, demonstrated the most prominent associations for rhinal and entorhinal tau outcomes. Among these participants, higher CPP (ß per SD, 0.45; 95% CI, 0.07-0.82; P = .02), FWA (ß per SD, 0.40; 95% CI, 0.06-0.74; P = .02), and CFPWV (ß per SD, 0.92; 95% CI, 0.40-1.44; P = .001) were associated with higher entorhinal tau burden, whereas higher CPP (ß per SD, 0.86; 95% CI, 0.01-0.72; P = .046), FWA (ß per SD, 0.33; 95% CI, 0.002-0.65; P = .049) and CFPWV (ß per SD, 0.86; 95% CI, 0.38-1.35; P <.001) were associated with higher rhinal tau burden. These associations were not significant among younger participants.

Age stratum-specific associations for inferior temporal tau outcomes were not significant; however, investigators did observe that higher CFPWV was associated with lower amygdala tau burden among younger (ß per SD, –0.22; 95% CI, –0.41 to –0.03; P = .02) but not older participants. Additionally, higher CPP was associated with higher inferior temporal tau burden among participants classified as apolipoprotein ε4 positive (ß per SD, 0.39; 95% CI, 0.02-0.76; P = .04). These findings were consistent with a study by Baek et al, who recently showed that progressive tau accumulation was more pronounced among APOE ε4 carriers, particularly within the temporal cortex.

REFERENCE
1. Cooper LL, O’Donnell A, Beiser A, et al. Association of aortic stiffness and pressure pulsatility with global amyloid-ß and regional tau burden among Framingham Heart Study participants without dementia. JAMA Neurol. 2022;79(7):710-719. doi:10.1001/jamaneurol.2022.1261.
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