. Arterial stiffness and β-amyloid progression in nondemented elderly adults. JAMA Neurol. 2014 May;71(5):562-8. PubMed.


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  1. Our group has demonstrated that interstitial fluid and solutes are cleared from the brain by bulk flow along the basement membranes of capillary and artery walls, analogous to the lymphatics of other organs (1). In aging, fibrils of amyloid accumulate in the basement membranes of cerebral arteries as cerebral amyloid angiopathy (CAA), suggesting that with increasing age there is a failure of elimination of solutes such as Aβ from the central nervous system (2, 3). The work by Timothy Hughes and colleagues provides substantive evidence to our experimental results, demonstrating that arterial stiffness measured by pulse wave velocity correlates with the accumulation of Aβ in the brain, increasing with age. Our mathematical models suggest that pulsations together with biochemical interactions provide the biophysical force necessary for the clearance of Aβ along the cerebrovascular basement membranes (4, and Keith Sharp et al., submitted). Despite the relatively small numbers of patients assessed in the study by Hughes and colleagues, it provides the rationale for assessing markers of peripheral arterial elasticity or stiffness as early biomarkers for the onset and progression of dementia.


    . Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol. 2008 Apr;34(2):131-44. Epub 2008 Jan 16 PubMed.

    . Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain. Aging Cell. 2013 Apr;12(2):224-36. PubMed.

    . Cerebral amyloid angiopathy, Prion angiopathy, CADASIL and the spectrum of Protein Elimination-Failure Angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol Appl Neurobiol. 2013 Mar 13; PubMed.

    . Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol. 2006 Feb 21;238(4):962-74. PubMed.

  2. The study by Hughes and colleagues highlights the utility of longitudinal amyloid imaging and pulse wave velocity (PWD) to measure arterial stiffness. By capitalizing on the relatively consistent age-related upward trajectory of PWD, the authors demonstrate that arterial stiffness is dynamically associated with increasing amyloid aggregation. Simply put, this article suggests that arterial stiffness is not just related to the amount of Aβ in the brain, but also the rate of Aβ aggregation. Many participants had significant Aβ deposition prior to measurement of PWD; therefore determining the initiating variable, Aβ or arterial stiffness, cannot be done. Nonetheless these findings are exciting because they take us a step further in explaining how specific components of the vascular system, i.e. central and peripheral measures of arterial stiffness, may be associated with Aβ deposition.

  3. This extremely interesting research points out the existence of a close correlation between capillary and microcirculatory blood flow in the brain and the process of amyloid accumulation in the cerebral tissue. The authors say that the deterioration of capillary blood flow enhances the deposition of amyloid in the cerebral tissue. These studies confirm our earlier work [1, 2, 3] that showed the presence of dyscirculatory angiopathy of Alzheimer's type (DAAT) in patients with AD, which leads to serious disorders of capillary blood flow in the brain and not only promotes the accumulation of Aβ in the cerebral tissue but also reduces its excretion, which was noted by Professor B. Zlokovic as well [4]. 


    . Dyscirculatory Angiopathy of Alzheimer's Type. J Behav Brain Sci 2011;1(2):57-68.

    . Vascular factors in Alzheimer’s disease. Health. 2012 Sep; 4(9A):735-42.

    . Disorders of cerebrovascular angioarchitectonics and microcirculation in the etiology and pathogenesis of Alzheimer’s disease. Adv Alzheimer Dis. 2013 Dec;(2)4:171-181.

    . Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci. 2011 Dec;12(12):723-38. PubMed.

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  1. Can Arterial Health Predict Amyloid Deposition?