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dc.contributor.authorEwers, Michael
dc.contributor.authorMielke, Michelle M
dc.contributor.authorHampel, Harald
dc.date.accessioned2012-02-01T10:48:31Z
dc.date.available2012-02-01T10:48:31Z
dc.date.issued2012-02-01T10:48:31Z
dc.identifier.citationExp Gerontol. 2010 Jan;45(1):75-9. Epub 2009 Sep 24.en_GB
dc.identifier.issn1873-6815 (Electronic)en_GB
dc.identifier.issn0531-5565 (Linking)en_GB
dc.identifier.pmid19782124en_GB
dc.identifier.doi10.1016/j.exger.2009.09.005en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207866
dc.description.abstractSporadic 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.
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAlzheimer Disease/*metabolism/*pathologyen_GB
dc.subject.meshBiological Markers/*metabolismen_GB
dc.subject.meshBrain/blood supply/metabolism/pathologyen_GB
dc.subject.meshCognition Disorders/metabolism/pathologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMicrovessels/*metabolism/*pathologyen_GB
dc.titleBlood-based biomarkers of microvascular pathology in Alzheimer's disease.en_GB
dc.contributor.departmentDiscipline 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.ieen_GB
dc.identifier.journalExperimental gerontologyen_GB
dc.description.provinceLeinster
html.description.abstractSporadic 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.


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