Blood-based biomarkers of microvascular pathology in Alzheimer's disease.
AffiliationDiscipline 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. firstname.lastname@example.org
MetadataShow full item record
CitationExp Gerontol. 2010 Jan;45(1):75-9. Epub 2009 Sep 24.
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.
- Alzheimer's disease.
- Authors: De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV
- Issue date: 2012
- Microvascular changes in Down syndrome with Alzheimer's-type pathology: Insights into a potential vascular mechanism for Down syndrome and Alzheimer's disease.
- Authors: Drachman DA, Smith TW, Alkamachi B, Kane K
- Issue date: 2017 Dec
- Spreading of amyloid, tau, and microvascular pathology in Alzheimer's disease: findings from neuropathological and neuroimaging studies.
- Authors: Thal DR, Attems J, Ewers M
- Issue date: 2014
- MRI and CSF studies in the early diagnosis of Alzheimer's disease.
- Authors: de Leon MJ, DeSanti S, Zinkowski R, Mehta PD, Pratico D, Segal S, Clark C, Kerkman D, DeBernardis J, Li J, Lair L, Reisberg B, Tsui W, Rusinek H
- Issue date: 2004 Sep
- Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer's disease.
- Authors: Hunter JM, Kwan J, Malek-Ahmadi M, Maarouf CL, Kokjohn TA, Belden C, Sabbagh MN, Beach TG, Roher AE
- Issue date: 2012