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Does Mutation That Protects Against Alzheimer s Increase Parkinson s Risk?

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A recent meta-analysis of 22 studies found that a variant in the apoliprotein E gene that protects against Alzheimer’s disease increases by 20 percent the risk of developing Parkinson’s disease.

The study of the variant, APOE-2, “basically shows that neurodegenerative diseases may differ in significant risk factors, contrary to prevailing views,” Xuemei Huang, assistant professor of neurology at the University of North Carolina, Chapel Hill, School of Medicine, said in a statement.

It is widely known that there are three alleles of the APO gene: APOE-2, -3 and -4. These and other APO genes transcribe apolipoproteins, which are involved in lipid metabolism. In addition, the APOE gene family is associated with longevity “and is more likely to be found in centenarians,” Huang added.

Yet APOE-4 is a “major susceptibility” gene for sporadic and familial Alzheimer’s disease, and has even been associated with poor clinical outcome in people with acute head injury and stroke.

“On the other hand,” APOE-2 “seems to occur with lower frequency” in individuals with Alzheimer’s disease, and is “linked” with symptoms of late-onset Alzheimer’s. Consequently, APOE-4 “was perceived as the ‘bad guy’ in neurological diseases, while APOE-2 was thought the ‘good guy,’” said Huang.

“Although most people in the field believed this, the results of individual studies generally had not shown a significant link between APOE alleles and Parkinson’s disease,” she added. Small studies “may not have had enough statistical power to detect any links between [APOE-2] and Parkinson’s.”

To get around this, Huang and co-author Charles Poole, associate professor of epidemiology in UNC’s School of Public Health, performed a meta-analysis of 22 studies that followed more than 2,000 Parkinson’s patients and nearly 8,000 controls. The team included only those studies that had “both clear clinical or pathologic criteria” for Parkinson’s and the necessary APOE genotype data.

The results of their study, which appear in the June issue of Neurology, found that APOE-2 “conveyed a slight but statistically significant risk for Parkinson’s disease, with an odds ratio of 1.2,” Huang said in the statement. Since the overall prevalence of Parkinson’s in the general population is about 1 percent, the findings show that the prevalence of the disease in individuals with APOE-2 is about 1.2 percent.”

The researchers stressed that the APOE-4 form of the gene is not a risk factor in Parkinson’s disease.

— KL

 

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