Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins

Lancet. 2004 Apr 3;363(9415):1139-46. doi: 10.1016/S0140-6736(04)15900-X.


Late-onset sporadic Alzheimer's disease is a heterogeneous disorder. In elderly patients, increasing evidence suggests a link between this neurodegenerative disease, and vascular risk factors and atherosclerosis. The nature of this link remains speculative. Some investigators have suggested that the disease arises as a secondary event related to atherosclerosis of extracranial or intracranial vessels. A toxic effect of vascular factors on the microvasculature of susceptible brain regions has also been argued. An alternative explanation is that atherosclerosis and Alzheimer's disease are independent but convergent disease processes. This hypothesis is lent support by observations of shared epidemiology, pathophysiological elements, and response to treatment in both disorders. It provides a potential framework for an improved understanding of the pathogenesis of Alzheimer's disease, especially in elderly patients with vascular risk factors, and offers some promise toward the search for preventive and therapeutic treatments.

Publication types

  • Review

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / physiopathology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arteriosclerosis / complications*
  • Arteriosclerosis / drug therapy
  • Arteriosclerosis / physiopathology
  • Aspirin / therapeutic use
  • Cholesterol / blood*
  • Cholesterol / physiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / physiopathology
  • Indomethacin / therapeutic use
  • Intracranial Arteriosclerosis / complications
  • Intracranial Arteriosclerosis / drug therapy
  • Intracranial Arteriosclerosis / physiopathology
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Vasculitis, Central Nervous System / complications*
  • Vasculitis, Central Nervous System / drug therapy
  • Vasculitis, Central Nervous System / physiopathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol
  • Aspirin
  • Indomethacin