Genes linked to Alzheimer's risk, resilience identified
CHICAGO. KAZINFORM An international team of researchers led by scientists at Washington University School of Medicine in St. Louis has identified a pair of genes that influence risk for both late-onset and early-onset Alzheimer's disease.
In thestudy, the researchers measured soluble TREM2 levels in the cerebrospinal fluidof 813 older adults, most of whom were aged 55 to 90. Of those subjects, 172had Alzheimer's disease, 169 were cognitively normal, and another 183 had earlymild cognitive impairment, Xinhua reports.
TREM2 is aprotein that is believed to help microglia cells clear excessive amounts of theAlzheimer's proteins amyloid and tau from the brain.
Theresearchers also analyzed the participants' DNA, conducting genomewideassociation studies to look for regions of the genome that may influence TREM2levels in the cerebrospinal fluid.
Commonvariants in the MS4A4A gene had been associated with risk for Alzheimer's, andthe study also connects those genes.
«Weobserved TREM2 risk variants more often in people who had Alzheimer's or weremildly cognitively impaired, compared with those who were cognitivelynormal,» said co-senior investigator Celeste Karch, an assistant professorin the Department of Psychiatry at Washington University in St. Louis. «Itturns out that about 30 percent of the population in the study had variationsin the MS4A4A gene that appear to affect their risk for developing Alzheimer'sdisease. Some variants protected people from Alzheimer's or made them moreresilient while others increased their risk.»
Diggingfurther, the researchers found that variants in the MS4A4A gene cluster linkedto an increase in risk for developing Alzheimer's disease are associated withlower levels of soluble TREM2 protein. The other variant, associated withhigher levels of TREM2 in the cerebrospinal fluid, seemed to protect againstAlzheimer's.
Theyvalidated the results in DNA from another 580 older adults. Once again, theyfound that higher soluble TREM2 levels in the cerebrospinal fluid seemedprotective, while lower levels increased risk. And those protein levels,whether high or low, were linked to variants in the MS4A4A gene.
«Forthe past several years, we've been looking at TREM2 and increasing our focus onthe involvement of the brain's immune cells in Alzheimer's disease,» saidBruno A. Benitez, an assistant professor of psychiatry. «These findingsgive us a new therapeutic strategy to pursue, one focusing not only on neuronsbut on how the microglia may be involved in helping to clear damaging proteins,such as beta amyloid and tau, that are linked to Alzheimer's disease.»
Those genevariants also may play a role in other diseases of the central nervous system,according to Laura Piccio, an associate professor of neurology and anotherco-senior author.
«Bycombining large genetic and spinal fluid analyses with laboratory work, we haveprovided strong evidence of a biological link between TREM2 and proteins in theMS4A gene cluster, both of which previously had been associated withAlzheimer's disease,» Piccio said. «We are beginning to elucidate amolecular pathway in microglia that could be critical not only in Alzheimer'sdisease but also in other neurodegenerative and inflammatory diseases in thecentral nervous system.»
The resultscould provide researchers with new targets and a strategy for delaying theonset of Alzheimer's symptoms.
Thefindings were published online in the journal Science Translational Medicine onWednesday.