Despite suggestions to the contrary in recent years, Alzheimer's and Parkinson's diseases do not appear to be part of a biological continuum, researchers reported.
A large-scale analysis found no evidence of common genetic regions that increase the risk of both illnesses, according to Valentina Moskvina, PhD, of the Cardiff University School of Medicine in Wales, and colleagues.
If there is pathological overlap between the two diseases, Moskvina and colleagues concluded online in JAMA Neurology, it must lie "downstream" of any of the major genes that increase the risk of each disease.
Although the two illnesses are clinically distinct, there have been suggestions they might be connected biologically.
Some reports have found Alzheimer's pathology in patients with Parkinson's and vice-versa, Moskvina and colleagues noted, while some genetic studies have found hints that the two diseases are linked.
And it's not impossible that seemingly distinct clinical entities have a common biological basis; a recent report found that five psychiatric entities share a common genetic underpinning.
In the case of Parkinson's and Alzheimer's, the search for genetic causes has uncovered several regions of the genome that appear to be risk factors for each disease.
But it has not been clear, the researchers noted, whether there are so-called "pleiotropic" genetic loci that might give rise to either disease, depending on other factors.
To help fill the gap, they conducted a meta-analysis of two recent genome-wide association studies, one in Alzheimer's and one in Parkinson's.
The Alzheimer's study included 3,177 patients and 7,277 controls, while the Parkinson's study had 5,333 patients and 12,298 controls.
Moskvina and colleagues analyzed the data three ways:
- By comparing genome-wide results from the combined dataset with those from the original analyses.
- By looking for potentially "polygenic" regions that would not have a significant effect individually but that might combine to increase risk.
- And by looking for genes that might contain multiple single nucleotide polymorphisms, some of which would confer a risk for Alzheimer's and some for Parkinson's.
But all three approaches came up negative. The "detailed interrogation ... resulted in no significant evidence" that supported the notion that there are some genetic regions that increase the risk of both diseases, Moskvina and colleagues wrote.
"Our findings therefore imply that loci that increase the risk of both (Parkinson's and Alzheimer's) are not widespread and that the pathological overlap could instead be 'downstream' of the primary susceptibility genes that increase the risk of each disease," they concluded.
On the other hand, they cautioned that they excluded patients with Lewy body dementia, which shares characteristics of both Alzheimer's and Parkinson's, and that may have limited the power of the analysis.
Also, they noted, it remains possible that future, more refined methods might yet find a common genetic basis for the disease.
The study had support from Parkinson's United Kingdom, the Medical Research Council, the Department of Health National Institute for Health Research Biomedical Research Centre, the German National Genome Network, the German Ministry for Education and Research, the NIH, the French National Agency of Research, and the National Research Funding Agency in the ERA-NET NEURON framework.
The journal said the authors made no disclosures.
- Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner