Cited by 122Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsBarrier Structure and Function Studies

Cerebrospinal Fluid Biomarkers of Neurovascular Dysfunction in Mild Dementia and Alzheimer'S Disease

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Sweeney, Melanie D, Sagare, Abhay P, Zlokovic, Berislav V·2015·Journal of Cerebral Blood Flow & Metabolism

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.

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  • Increasing evidence supports that early cerebrovascular dysfunction contributes to AD pathophysiology and cognitive impairment.

    “In addition to the classic hallmark pathology, A 𝛃 plaques, hyperphosphorylated tau neurofibrillary tangles, and neuron loss, increasing evidence supports that early cerebrovascular dysfunction contributes to AD pathophysiology and cognitive impairment (29, 285, 418, 421, 429, 569, 571, 593, 682, 693).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [571]

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  1. 9Montine T. Conference and recommendations report to the NINDS Council. Bethesda, Maryland. 2013. http://www.ninds.nih.gov/funding/areas/neurodegeneration/workshops/adrd2013/ADRD_2013_Report-and-Memorandum_508comp.pdf (accessed 22 Jan 2014).

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Authors
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V.
Affiliations
  • University of Southern California (US)
  • Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Venue
Journal of Cerebral Blood Flow & Metabolism
Published
2015-04-22
Volume
35
Issue
7
Pages
1055-1068
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
OpenAlex
W1977604869
Cited by
122
References
224
Citations by year
2026: 3 · 2025: 8 · 2024: 12 · 2023: 7 · 2022: 13 · 2021: 13 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 8
FWCI
1.84
Type
journal article
Language
en
Open access
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (R01AG023084, R01AG039452, AG23084, R37AG023084, AG039452, P50AG005142, RF1AG039452)
  • National Institute of Neurological Disorders and Stroke (R37NS034467, NS34467, R01NS034467)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
Alzheimer's disease, mild dementia, cerebrospinal fluid biomarkers, neurovascular unit, vascular dysfunction, amyloid-beta, tau protein, endothelial cells, pericytes, vascular smooth muscle cells, astrocytes, microglia, early detection
MeSH terms
Alzheimer Disease, Animals, Astrocytes, Brain, Dementia, Diet, Humans, Stress, Physiological, Biomarkers, Exercise, Microglia, Pericytes, Endothelial Cells

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