Beta-amyloid, blood vessels, and brain function

Abstract

Cerebrovascular disease and Alzheimer disease are common diseases of aging and frequently coexist in the same brain. Accumulating evidence suggests that the presence of brain infarction, including silent infarction, influences the course of Alzheimer disease. Conversely, there is evidence that beta-amyloid can impair blood vessel function. Vascular beta-amyloid deposition, also known as cerebral amyloid angiopathy, is associated with vascular dysfunction in animal and human studies. Alzheimer disease is associated with morphological changes in capillary networks, and soluble beta-amyloid produces abnormal vascular responses to physiological and pharmacological stimuli. In this review, we discuss current evidence linking beta-amyloid metabolism with vascular function and morphological changes in animals and humans.

Figures

Figure 1

Beta-amyloid (Aβ) production and clearance. Amyloid precursor protein (APP) undergoes proteolytic cleavage by alpha- and gamma-secretase to yield a 40 amino acid fragment (Aβ40) or 42 amino acid fragment (Aβ42). Possible fates include parenchymal or vascular deposition as amyloid, proteolytic cleavage, perivascular drainage or efflux across the blood-brain barrier. CAA, cerebral amyloid angiopathy.

Figure 2

Examples of visual evoked flow in the posterior cerebral artery (PCA) in a 77 year old control subject and a 73 year old subject with cerebral amyloid angiopathy (CAA). A 10 Hz flashing checkerboard stimulus was viewed during the “on” period. The curves represent averages of ten 40-second epochs. The peak increase from baseline in the PCA (“PCA peak response”) was 20% in the control subject and 14% in the CAA subject. In the study, mean peak PCA response was 8.0±6.7% in 11 CAA patients compared to 17.4±5.7% in 9 controls (p=0.002).