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Breakdown of the Cerebrovasculature and Blood-Brain Barrier: A Mechanistic Link Between Diabetes Mellitus and Alzheimer's Disease.
Journal of Alzheimer's Disease (2016)
  • Eric L. Goldwaser, Rowan University School of Osteopathic Medicine
  • Nimish K. Acharya, Rowan University School of Osteopathic Medicine
  • Abhirup Sarkar, Rowan University School of Osteopathic Medicine
  • George Godsey, Rowan University School of Osteopathic Medicine
  • Robert G. Nagele, Rowan University School of Osteopathic Medicine
Abstract
Alzheimer's disease (AD) and diabetes mellitus (DM) are among the most pervasive and devastating disorders that afflict people throughout the world. Although typically associated with older demographics, recent epidemiologic studies have reported parallel trends in decreasing age of onset and increasing incidence of these conditions. Promising research continues to implicate the cerebrovasculature and blood-brain barrier (BBB) as playing key roles in AD pathoetiology. Similarly, complications accompanying DM, such as diabetic nephropathy/retinopathy, cardiovascular disease, and stroke, have been rooted in vascular compromise. Not surprisingly, DM is now considered a major risk factor for AD. The purpose of this review is to highlight investigations into the role of the cerebrovasculature in the development and progression of AD. We give particular attention to studies on humans and a variety of animal model systems that have demonstrated a link between BBB dysfunction and pathological changes in the brain consistent with aging and AD. Together, these studies suggest that the vascular complications associated with chronic, poorly managed DM can lead to subclinical BBB breakdown that precedes and drives the pathological changes progressing to symptomatic AD, providing a common mechanistic thread connecting these two disorders. Furthermore, this emphasizes the need to focus on the vasculature as a potential therapeutic target with the intent of limiting BBB breakdown involved in disease initiation and progression. In conclusion, AD may be more than just an associated comorbidity of DM, and instead another manifestation of the underlying vascular pathology that is common to both.
Keywords
  • Alzheimer’s disease,
  • amyloid,
  • blood-brain barrier,
  • dementia,
  • diabetes complications,
  • diabetes mellitus
Publication Date
September 6, 2016
DOI
10.3233/JAD-160284
Citation Information
Eric L. Goldwaser, Nimish K. Acharya, Abhirup Sarkar, George Godsey, et al.. "Breakdown of the Cerebrovasculature and Blood-Brain Barrier: A Mechanistic Link Between Diabetes Mellitus and Alzheimer's Disease." Journal of Alzheimer's Disease Vol. 54 Iss. 2 (2016) p. 445 - 456
Available at: http://works.bepress.com/nimish-acharya/4/