Cerebral Hypoperfusion and the Energy Deficit in Alzheimer's Disease

Seth Love*, J. Scott Miners

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

32 Citations (Scopus)
346 Downloads (Pure)


There is a perfusion deficit in Alzheimer's disease (AD), commencing in the precuneus and spreading to other parts of the cerebral cortex. The deficit anticipates the development of dementia, contributes to brain damage, and is caused by both functional and structural abnormalities of the cerebral vasculature. Most of the abnormalities are probably secondary to the accumulation of Aβ but the consequent hypoperfusion may, in turn, increase Aβ production. In the early stages of disease, abnormalities that cause vasoconstriction predominate. These include cholinergic vascular denervation, inhibition of endothelial nitric oxide synthase, increased production of endothelin-1 production and possibly also of angiotensin II. Patients with AD also have an increased prevalence of structural disease of cerebral microvessels, particularly CAA and capillary damage, and particularly in the later stages of disease these are likely to make an important contribution to the cerebral hypoperfusion. The metabolic abnormalities that cause early vascular dysfunction offer several targets for therapeutic intervention. However, for intervention to be effective it probably needs to be early. Prolonged cerebral hypoperfusion may induce compensatory circulatory changes that are themselves damaging, including hypertension and small vessel disease. This has implications for the use of antihypertensive drugs once there is accumulation of Aβ within the brain.

Original languageEnglish
Pages (from-to)607-617
Number of pages11
JournalBrain Pathology
Issue number5
Early online date26 Sep 2016
Publication statusPublished - Sep 2016


  • Alzheimer's disease
  • amyloid-β peptide
  • capillary damage
  • cerebral amyloid angiopathy
  • cholinergic innervation
  • endothelial nitric oxide synthase
  • endothelin-1
  • hypoperfusion
  • ischemia
  • renin-angiotensin system
  • vascular dysfunction

Fingerprint Dive into the research topics of 'Cerebral Hypoperfusion and the Energy Deficit in Alzheimer's Disease'. Together they form a unique fingerprint.

Cite this