A Comparison of Apolipoprotein E Polymorphism in Alzheimer's Disease and Subcortical Vascular Dementia in Koreans

Abstract

INTRODUCTIONThe apolipoprotein E gene (Apo E) is located on the 19th chromosome and has 3 alleles, which are ε2, ε3, and ε4.1 Previous studies showed that the Apo E ε4 allele is a risk factor that increases the risk of sporadic Alzheimer's disease (AD) and late-onset AD in addition to decreasing the age of onset. Although disputable, some studies have suggested that Apo E ε4 is related to a high level of low density lipoprotein and may affect nervous system diseases associated with vascular injuries.2,3 Also, vascular pathology has been repeatedly reported in late-stage AD patients. It is also reported that cerebrovascular and cardiovascular risk factors can enhance the progress of AD. In this way, many recent studies have suggested that vascular factors may be common etiologic factors of both AD and vascular dementia (VaD). Subcortical vascular dementia (SVaD) is known to be caused by microangiopathy within the deep brain. SVaD can be divided into arteriosclerotic leukoencephalopathy (Binswanger type), which contains the etiologic factor in the white matter, and multiple subcortical lacunar lesion (lacunar type), which is caused by multiple infarction of deep brain gray matter.Likewise, considering the effect of Apo E ε4 lipid metabolism and the common vascular etiologic factor found in AD Background and Purpose The apolipoprotein E (Apo E) ε4 allele is known to be a risk factor for Alzheimer's disease (AD). However, there are debates about the relationship between Apo E ε4 frequency and subcortical vascular dementia (SVaD). We compared the frequency of the Apo E ε4 allele in AD and SVaD in Koreans.Methods The study was comprised of 400 subjects who visited the Dementia Clinic at Daegu Catholic University from July 2007 to December 2011. Neuropsychological tests, a brain MRI, and blood laboratory tests were performed on all subjects. Two hundred and ninety subjects were AD, 32 subjects were SVaD and 78 subjects were normal. The diagnosis for SVaD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and Erkinjuntti criteria, and the diagnosis for AD was based on the DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's disease and Related Disorders Association criteria. Apo E polymorphism was genotyped in all subjects. ResultsThe Apo E ε4 allele frequency was 17.4% in AD, 10.9% in SVaD and 8.3% in the normal group (p=0.03). The odds ratio (OR) after age adjustment for AD conferred to the Apo E ε4 was 2.04 (p=0.04). But, the OR for SVaD conferred to the Apo E ε4 allele was 1.34 (p=0.62), indicating that the Apo E ε4 allele does not significantly confer the risk of SVaD.Conclusions Apo E ε4 is a reliable predictor of AD but has modest efficacy for predicting SVaD in Koreans.