Vascular dysfunction—The disregarded partner of Alzheimer's disease

Melanie D. Sweeney, Axel Montagne, Abhay P. Sagare, Daniel A. Nation, Lon S. Schneider, Helena C. Chui, Michael G. Harrington, Judy Pa, Meng Law, Danny J. J. Wang, Russell E. Jacobs, Fergus N. Doubal, Joel Ramirez, Sandra E. Black, Maiken Nedergaard, Helene Benveniste, Martin Dichgans, Costantino Iadecola, Seth Love, Philip M. BathHugh S. Markus, Rustam A. Salman, Stuart M. Allan, Terence J. Quinn, Rajesh N. Kalaria, David J. Werring, Roxana O. Carare, Rhian M. Touyz, Steve C. R. Williams, Michael A. Moskowitz, Zvonimir S. Katusic, Sarah E. Lutz, Orly Lazarov, Richard D. Minshall, Jalees Rehman, Thomas P. Davis, Cheryl L. Wellington, Hector M. González, Chun Yuan, Samuel N. Lockhart, Timothy M. Hughes, Christopher L. H. Chen, Perminder Sachdev, John T. O'Brien, Ingmar Skoog, Leonardo Pantoni, Deborah R. Gustafson, Geert Jan Biessels, Anders Wallin, Eric E. Smith, Vincent Mok, Adrian Wong, Peter Passmore, Frederick Barkof, Majon Muller, Monique M. B. Breteler, Gustavo C. Román, Edith Hamel, Sudha Seshadri, Rebecca F. Gottesman, Mark A. van Buchem, Zoe Arvanitakis, Julie A. Schneider, Lester R. Drewes, Vladimir Hachinski, Caleb E. Finch, Arthur W. Toga, Joanna M. Wardlaw, Berislav V. Zlokovic

Research output: Contribution to journalArticleAcademicpeer-review

381 Citations (Scopus)


Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.
Original languageEnglish
Pages (from-to)158-167
Number of pages10
JournalAlzheimer's and Dementia
Issue number1
Publication statusPublished - 2019


  • Alzheimer's disease
  • Biomarkers
  • Blood-brain barrier
  • Cerebral blood flow
  • MRI
  • Vascular

Cite this