Increased tau burden is observed in abnormal central vascular hemodynamics

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

Lead researcher Leroy Cooper, PhD, MH, assistant professor of biology at Vassar College and colleagues concluded that “aortic stiffness is likely modifiable and thus represents a likely independent target for prevention of tau-related disease.”

Posted in gamma neurology, The study included 257 middle-aged and older adults without dementia who had successfully undergone a comprehensive hemodynamic assessment and were considered on the vascular risk scale. After positron emission tomography (PET) scans, tonometry was used to assess measures of aortic stiffness and pulse pressure, including carotid and femoral pulse wave velocity (CFPWV), central pulse pressure (CPP) and frontal wave amplitude (FWA).

The study also used a compound C-Pittsburgh B (PiB) and 18F-flortaucipir (FTP) for assessment of amyloid-β (Aß) plaque burden and tau protein deposition in the brain, respectively. Participants in the top five Aß quintiles (≥ 1.09 PiB share size distribution) were rated as positive for a high Aß burden. FTP retention in the nasal cortex was assessed using head surface mapping of the cortical stripe at the midpoint of the gray matter.

The results on multivariate models showed that the increase of CPP (ß for each standard deviation [SD], 0.17; SE, 0.09; 95% CI, 0.01-0.32; s = .03) with increased internal olfactory tau burden. In similar models, the cost-per-page (CPP) was higher (ß per SD, 0.19; SE, 0.09; 95% CI, 0.02–0.36; s = .03) and FWA (ß per SD, 0.17; SE, 0.08; 95% CI, 0.01–0.32; s = .03) with increasing rhinal tau burden. Measures of aortic stiffness and pulse pressure were not related to the amygdala, inferior temporal burden, and primary burden, and were not related to the Aß burden.

Older participants, aged 60 years and over, showed the most significant associations for tau rhinal and entorhinal scores. Among these participants, the CPP was higher (ß per SD, 0.45; 95% CI, 0.07–0.82; s = .02), FWA (ß per SD, 0.40; 95% CI, 0.06–0.74; s = .02) and CFPWV (ß per SD, 0.92; 95% CI, 0.40–1.44; s = .001) was associated with a higher intrinsic waxy tau burden, while a higher CPP (ß per SD, 0.86; 95% CI, 0.01–0.72; s = .046), FWA (ß per SD, 0.33; 95% CI, 0.002-0.65; s = .049) and CFPWV (ß per SD, 0.86; 95% CI, 0.38–1.35; s <.001) with high rhinal tau burden. These associations were not significant among the younger participants.

The age-class correlations of inferior temporal tau scores were not significant; However, the authors noted that higher CFPWV was associated with lower amygdala tau burden among the younger ones (ß per SD, -0.22; 95% CI, -0.41 to -0.03; s = .02) but not the oldest participants. In addition, higher CPP was associated with higher lower temporal tau burden among participants classified as ε4-positive lipoprotein (ß per SD, 0.39; 95% CI, 0.02–0.76; s = .04). These results were consistent with a study by Baek et al, who recently showed that gradual 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 pulse pressure with global amyloid beta and regional tau burden among participants in the Framingham Heart Study without dementia. Gamma Neurol. 2022; 79 (7): 710-719. doi: 10.1001/jamaneurol.2022.1261.