A team of researchers has discovered a new gene that is associated with Tau accumulation, which is one of the defining features of Alzheimer disease (AD).
Investigators at BWH and Rush University Medical Center described the identification and validation of a genetic variant within the protein tyrosine phosphatase receptor-type delta (PTPRD) gene.
Tau accumulates in several different conditions in addition to AD, including certain forms of dementia and Parkinsonian syndromes as well as chronic traumatic encephalopathy that occur with repeated head injuries.
“Aging leads to the accumulation of many different pathologies in the brain; one of the most common forms of pathology is the neurofibrillary tangle (NFT) that was at the center of our study,” said co-principal investigator David Bennett. “The NFT is thought to be more closely related to memory decline than other forms of aging-related pathologies, but there are still very few genes that have been implicated in the accumulation of this key feature of Alzheimer disease and other brain diseases.”
Leveraging autopsies from 909 individuals participating in studies of aging based at Rush University, the team of investigators assessed the human genome for evidence that a genetic variant could affect NFT.
Lead author Lori Chibnik said, “The variant that we discovered is common: most people have one or two copies of the version of the gene that is linked to accumulating more pathology as you get older. Interestingly, tangles can accumulate through several different mechanisms, and the variant that we discovered appears to affect more than one of these mechanism.”
{{/usCountry}}Lead author Lori Chibnik said, “The variant that we discovered is common: most people have one or two copies of the version of the gene that is linked to accumulating more pathology as you get older. Interestingly, tangles can accumulate through several different mechanisms, and the variant that we discovered appears to affect more than one of these mechanism.”
{{/usCountry}}The reported results offer an important new lead as the field of neurodegeneration searches for robust novel targets for drug development. In addition, the advent of new techniques to measure Tau in the brains of living individuals with positron emission tomography (PET) offers a biomarker for therapies targeting Tau.
The study is published in Molecular Psychiatry.
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