Your browser doesn't support javascript.
loading
Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction.
Nation, Daniel A; Sweeney, Melanie D; Montagne, Axel; Sagare, Abhay P; D'Orazio, Lina M; Pachicano, Maricarmen; Sepehrband, Farshid; Nelson, Amy R; Buennagel, David P; Harrington, Michael G; Benzinger, Tammie L S; Fagan, Anne M; Ringman, John M; Schneider, Lon S; Morris, John C; Chui, Helena C; Law, Meng; Toga, Arthur W; Zlokovic, Berislav V.
Afiliación
  • Nation DA; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sweeney MD; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Montagne A; Department of Psychology, University of Southern California, Los Angeles, CA, USA.
  • Sagare AP; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • D'Orazio LM; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Pachicano M; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sepehrband F; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Nelson AR; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Buennagel DP; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Harrington MG; Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Benzinger TLS; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Fagan AM; Huntington Medical Research Institutes, Pasadena, CA, USA.
  • Ringman JM; Huntington Medical Research Institutes, Pasadena, CA, USA.
  • Schneider LS; Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
  • Morris JC; The Hope Center for Neurodegenerative Disorders, Washington University School of Medicine, St. Louis, MO, USA.
  • Chui HC; The Hope Center for Neurodegenerative Disorders, Washington University School of Medicine, St. Louis, MO, USA.
  • Law M; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
  • Toga AW; The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Zlokovic BV; Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Nat Med ; 25(2): 270-276, 2019 02.
Article en En | MEDLINE | ID: mdl-30643288
ABSTRACT
Vascular contributions to cognitive impairment are increasingly recognized1-5 as shown by neuropathological6,7, neuroimaging4,8-11, and cerebrospinal fluid biomarker4,12 studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer's disease (AD)3,4,13. Vascular changes in AD have been typically attributed to the vasoactive and/or vasculotoxic effects of amyloid-ß (Aß)3,11,14, and more recently tau15. Animal studies suggest that Aß and tau lead to blood vessel abnormalities and blood-brain barrier (BBB) breakdown14-16. Although neurovascular dysfunction3,11 and BBB breakdown develop early in AD1,4,5,8-10,12,13, how they relate to changes in the AD classical biomarkers Aß and tau, which also develop before dementia17, remains unknown. To address this question, we studied brain capillary damage using a novel cerebrospinal fluid biomarker of BBB-associated capillary mural cell pericyte, soluble platelet-derived growth factor receptor-ß8,18, and regional BBB permeability using dynamic contrast-enhanced magnetic resonance imaging8-10. Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer's Aß and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aß and tau.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Biomarcadores / Disfunción Cognitiva Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Biomarcadores / Disfunción Cognitiva Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos