Homocysteine and Alzheimer's Disease

The search for modifiable risk factors for Alzheimer's disease has been intensive. Three risk factors previously identified for the disease are age, family history and the presence of a specific genetic trait termed APOE epsilon 4. Recently, Dr. Sudha Seshadri at Boston University reported that elevated Hcy is a risk factor for the development of Alzheimer's disease (N. Eng. J. Med, 346: Feb. 14, 2002). In the study, the investigators, using data from the Framingham Heart Study, found that 30% of people showing the highest tHcy levels had twice the risk of developing Alzheimer's disease as people with average levels, although even mild elevations appeared to add some Hcy and Alzheimer's Disease In a cross-sectional study, Muntner, et al., measured plasma tHcy levels in 16,000 patients in comparison with their glomerular filtration rate (GFR). After standardization for age, race or ethnicity, and sex, the estimated GFR was found to be strongly associated with higher levels of tHcy. When the patient group's average tHcy levels were higher than 32.5 μmol/L, their GFR rates were more than 5 times lower than patient groups with lower average tHcy levels (Figure 12). Figure 12 14 Prevalence of elevated Hcy in patients with chronic renal disease risk. The study concluded that elevated tHcy accounts for about 15% of the population's risk in developing Alzheimer's disease. This implies that if tHcy were entirely removed from the equation, 15% of cases may be preventable. Moreover, it was concluded a 40% increase in developing Alzheimer's disease was associated with each 5 μmol/L rise in tHcy levels.

Though the mechanism linking Hcy and Alzheimer's disease is poorly understood, it is possible that Hcy is toxic to brain cells, possibly by excessive stimulation, resulting in neuronal damage due to CNS ischemia (Figure 13).