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    Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

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    Authors
    Ewers, Michael
    Mielke, Michelle M
    Hampel, Harald
    Affiliation
    Discipline of Psychiatry, School of Medicine & Trinity College Institute of, Neuroscience, Laboratory of Neuroimaging & Biomarker Research, Trinity College,, University of Dublin, The Adelaide and Meath Hospital Incorporating The National , Children's Hospital, Tallaght, Dublin, Ireland. ewersm@tcd.ie
    Issue Date
    2012-02-01T10:48:31Z
    MeSH
    Aged
    Alzheimer Disease/*metabolism/*pathology
    Biological Markers/*metabolism
    Brain/blood supply/metabolism/pathology
    Cognition Disorders/metabolism/pathology
    Humans
    Microvessels/*metabolism/*pathology
    
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    Citation
    Exp Gerontol. 2010 Jan;45(1):75-9. Epub 2009 Sep 24.
    Journal
    Experimental gerontology
    URI
    http://hdl.handle.net/10147/207866
    DOI
    10.1016/j.exger.2009.09.005
    PubMed ID
    19782124
    Abstract
    Sporadic Alzheimer's disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.
    Language
    eng
    ISSN
    1873-6815 (Electronic)
    0531-5565 (Linking)
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.exger.2009.09.005
    Scopus Count
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    Tallaght University Hospital

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