Homocysteine and brain atrophy

Prog Neuropsychopharmacol Biol Psychiatry. 2005 Sep;29(7):1152-61. doi: 10.1016/j.pnpbp.2005.06.026.


Homocysteine (Hcy) has been implicated as a risk factor for vascular disease as well as brain atrophy. There is evidence to implicate Hcy in increased oxidative stress, DNA damage, the triggering of apoptosis and excitotoxicity, all important mechanisms in neurodegeneration. Hcy is also prothrombotic and proatherogenic, and causes damage to the vessel wall. It is related to brain atrophy in older individuals, and possibly to white matter hyperintensities (WMH) in the brain. Epidemiological evidence and longitudinal data support Hcy as a risk factor for cognitive impairment and Alzheimer's Disease (AD). This may be due to cerebrovascular as well as direct neurotoxic mechanisms. Its role in Parkinson Disease (PD) is less well supported. High Hcy has been suggested as a mediating factor in alcohol-related brain atrophy. The high prevalence of hyperhomocysteinemia in the population and its easy treatability make Hcy an interesting amino acid for future intervention studies in the prevention of degenerative brain disorders. Intervention studies are necessary to confirm its aetiological role.

Publication types

  • Review

MeSH terms

  • Alcoholism / metabolism
  • Alcoholism / pathology
  • Animals
  • Atrophy / metabolism
  • Brain Diseases / metabolism*
  • Brain Diseases / pathology*
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Homocysteine / metabolism*
  • Humans
  • Hyperhomocysteinemia / metabolism
  • Hyperhomocysteinemia / pathology


  • Homocysteine