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Alzheimer disease

Homocysteine and Alzheimer disease: an intervention study

Nature Reviews Neurology volume 7, pages 9–10 (2011)Cite this article

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Observational studies suggest that high homocysteine levels are a risk factor for brain atrophy and Alzheimer disease, but intervention studies have been inconclusive. New evidence that B vitamin therapy can slow brain atrophy will allow re-examination of elevated homocysteine levels as a potentially treatable risk factor for this disease.

The sulfur-containing amino acid homocysteine is of interest to neurologists for many reasons. Hyperhomocysteinemia—an abnormally high blood homocysteine level—was first recognized as a risk factor for vascular disease over 40 years ago. Since then, a steady stream of reports has linked homocysteine to atherosclerotic disease of coronary, cerebral and peripheral blood vessels, and also to microvascular disease, with implications for increased risk of stroke and small-vessel disease in the brain. Probable mechanisms for the vascular effects of elevated homocysteine levels include decreased activity of key antioxidant enzymes, increased generation of the superoxide anion, proinflammatory expression of tumor necrosis factor and inducible nitric oxide synthase, and endothelial dysfunction.1 Homocysteine-related microvascular disease possibly increases the deposition of amyloid-β plaques and the formation of neurofibrillary tangles, both of which are pathological features of Alzheimer disease (AD). Homocysteine is thought to promote apoptosis2 and to have a direct neurotoxic effect through its action on the N-methyl-D-aspartate glutamate receptor. In addition, its metabolite homocysteic acid has excitotoxic activity. Through these observations, one can begin to appreciate the substantial body of literature concerning the relationship between homocysteine and the risk of AD. Smith et al. have recently reported the beneficial effects of B vitamins in lowering high levels of homocysteine in patients with mild cognitive impairment (MCI).3

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  1. Brain and Ageing Research Program, School of Psychiatry, University of New South Wales, Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Barker Street, Randwick, NSW 2031, Sydney, Australia

    Perminder S. Sachdev

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Sachdev, P. Homocysteine and Alzheimer disease: an intervention study. Nat Rev Neurol 7, 9–10 (2011). https://doi.org/10.1038/nrneurol.2010.195

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