Apolipoprotein E and central nervous system disorders: Reviews of clinical findings
Version of Record online: 25 NOV 2010
© 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences
Volume 64, Issue 6, pages 592–607, December 2010
How to Cite
Takeda, M., Martínez, R., Kudo, T., Tanaka, T., Okochi, M., Tagami, S., Morihara, T., Hashimoto, R. and Cacabelos, R. (2010), Apolipoprotein E and central nervous system disorders: Reviews of clinical findings. Psychiatry and Clinical Neurosciences, 64: 592–607. doi: 10.1111/j.1440-1819.2010.02148.x
- Issue online: 25 NOV 2010
- Version of Record online: 25 NOV 2010
- Received 5 July 2010; revised 25 August 2010; accepted 1 September 2010.
- Alzheimer's disease;
- apolipoprotein E;
- genetic risk;
Dementia is a major health problem in developed countries with over 25 million people affected worldwide and probably over 75 million people at risk during the next 20 years. Alzheimer's disease (AD) is the most frequent cause of dementia (50–70%), followed by vascular dementia (30–40%), and mixed dementia (15–20%). AD pathogenesis is still to be elucidated but it is believed to be the complex interaction between genetic and environmental factors in later life. Three causative genes for familial AD have been identified: amyloid precursor protein, presenilin-1, and presenilin-2. There are 150 genes involved with increased neuronal vulnerability to premature death in the AD brain. Among these susceptibility genes, the apolipoprotein E (ApoE) gene is the most prevalent as a risk for AD pathogenic process in which complex interactions between genetic and environmental factors are involved, leading to a cascade of pathogenic events converging in final pathways to premature neuronal death. Some of these mechanisms are common to several neurodegenerative disorders that differ depending upon the genes affected and the involvement of environmental conditions.
ApoE is a key lipoprotein in lipid and cholesterol metabolism and it is also the major risk gene for AD and many other central nervous system disorders. The pathogenic role of ApoE-4 is still to be clarified; however, diverse evidence suggests that ApoE may play pleiotropic functions in dementia and central nervous system disorders.