Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease

J Cereb Blood Flow Metab. 2015 Jul;35(7):1055-68. doi: 10.1038/jcbfm.2015.76. Epub 2015 Apr 22.

Abstract

Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth muscle cells), glial cells (astrocytes and microglia), and neurons. Thus, identifying and integrating biomarkers of the NVU cell-specific responses and injury with established AD biomarkers, amyloid-β (Aβ) and tau, has a potential to contribute to better understanding of the disease process in dementias including AD. Here, we discuss the existing literature on cerebrospinal fluid biomarkers of the NVU cell-specific responses during early stages of dementia and AD. We suggest that the clinical usefulness of established AD biomarkers, Aβ and tau, could be further improved by developing an algorithm that will incorporate biomarkers of the NVU cell-specific responses and injury. Such biomarker algorithm could aid in early detection and intervention as well as identify novel treatment targets to delay disease onset, slow progression, and/or prevent AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Biomarkers / analysis
  • Biomarkers / cerebrospinal fluid*
  • Brain / blood supply
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology*
  • Dementia / cerebrospinal fluid*
  • Dementia / metabolism
  • Dementia / pathology
  • Dementia / physiopathology*
  • Diet
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Exercise
  • Humans
  • Microglia / metabolism
  • Microglia / pathology
  • Pericytes / metabolism
  • Pericytes / pathology
  • Stress, Physiological

Substances

  • Biomarkers