title: Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease.
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.
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Sweeney
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Abhay P
authors.initials: AP
authors.lastname: Sagare
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Berislav V
authors.initials: BV
authors.lastname: Zlokovic
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004032:Diet; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D015444:Exercise; D006801:Humans; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological
chemical_list: D015415:Biomarkers