Beta-amyloid plaque progression is pinned to arterial stiffness

The ongoing deposition of beta-amyloid in the aging brain is related to central arterial stiffness, according to a study published online March 31 in JAMA Neurology.

In addition to apolipoprotein E4, other major risk factors of developing neurodegenerative disease include amyloid deposition, tau and other neurotoxic protein aggregates, and now cardiovascular disease is becoming a mainstream focus. Yet, some studies have yielded contradicting evidence regarding the link between hypertension and neurodegeneration. This study focuses specifically on vascular stiffness as a risk factor for beta-amyloid progression.

“Central arterial stiffness tends to have a closer association with cerebrovascular disease,” wrote Kevin S. King, MD, author of study commentary also published in JAMA Neurology.

A team of researchers, including Timothy M. Hughes, PhD, from the department of internal medicine at Wake Forest School of Medicine and Wake Forest University in Winston-Salem, N.C., conducted a longitudinal observational study tracking the correlation of vascular stiffness and beta-amyloid burden for the non-demented elderly. Results of their study reflected a positive correlation between beta-amyloid progression as imaged by PET and C-11 Pittsburgh compound B (C-11 PiB) at baseline and two-year follow up and arterial stiffness as measured by pulse wave velocity at different areas of the body.

For this study, 81 patients aged 83 years or older without dementia were included in the study. After the two-year follow up, the researchers evaluated the C-11 PiB PET scans and found that the proportion of patients with beta-amyloid burden boomed from 48 percent to 75 percent.

Brachial-ankle pulse wave velocity, which represents a comparison of blood pressure between the upper arm and lower leg, was pitched only in subjects with higher amyloid deposition at the two-year mark. Central arterial stiffness was an independent indicator of higher amyloid burden, but the researchers are still trying to understand the connection.  

“The authors acknowledge that while beta-amyloid deposition and vascular stiffness appear to be associated, the mechanisms for this are not well established,” wrote Hughes, et al.

All of the patients carrying the apolipoprotein E4 allele were beta-amyloid positive by PET scan by the end of the study. Interestingly, beta-amyloid burden was not linked to history of heart disease or even associated with cerebrovascular disease at this point. However the researchers have suspicions about microvascular disease.

“Although we determined that Aβ deposition and vascular stiffness are associated, the pathophysiologic mechanisms involved in this process are not well established,” the researchers wrote. “Large artery stiffness has a direct effect on microvascular structure and function in the brain, resulting in cerebral hypoperfusion, which can lead to cognitive impairments. Alternatively, microvascular dysfunction may also lead to protein leakage, edema formation and damage to brain tissue, which may contribute to Aβ deposition.”

Further research is needed to fully understand how arterial stiffness and other factors affect the pathogenesis of brain disease.