Plasma osteopontin as a biomarker of Alzheimer's disease and vascular cognitive impairment

Sci Rep. 2021 Feb 17;11(1):4010. doi: 10.1038/s41598-021-83601-6.


Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer's disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined. Its correlations with inflammatory cytokines in cognitive impairment also await investigation. 80 subjects with no cognitive impairment (NCI), 160 with CIND and 144 with dementia were included in a cross-sectional study on a Singapore-based memory clinic cohort. All subjects underwent comprehensive clinical, neuropsychological and brain neuroimaging assessments, together with clinical diagnoses based on established criteria. Blood samples were collected and OPN as well as inflammatory cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF) were measured using immunoassays. Multivariate regression analyses showed significant associations between increased OPN and VCI groups, namely CIND with CeVD, AD with CeVD and VaD. Interestingly, higher OPN was also significantly associated with AD even in the absence of CeVD. We further showed that increased OPN significantly associated with neuroimaging markers of CeVD and neurodegeneration, including cortical infarcts, lacunes, white matter hyperintensities and brain atrophy. OPN also correlated with elevated levels of IL-6, IL-8 and TNF. Our findings suggest that OPN may play a role in both VCI and neurodegenerative dementias. Further longitudinal analyses are needed to assess the prognostic utility of OPN in disease prediction and monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / metabolism*
  • Atrophy / pathology
  • Biomarkers / blood
  • Brain / pathology
  • Case-Control Studies
  • Cerebrovascular Disorders / pathology
  • Cognition
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / metabolism*
  • Cohort Studies
  • Cross-Sectional Studies
  • Dementia, Vascular / diagnosis
  • Dementia, Vascular / metabolism
  • Dementia, Vascular / pathology
  • Female
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Interleukin-8 / analysis
  • Interleukin-8 / blood
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neuroimaging / methods
  • Osteopontin / blood
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • Singapore
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Diseases / pathology


  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • SPP1 protein, human
  • Tumor Necrosis Factor-alpha
  • Osteopontin