AANS Neurosurgeon | Volume 26, Number 2, 2017

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Study Details Molecular Roots of Alzheimer's

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Cellular ‘housekeeping’ molecule’s structure linked to neurodegeneration¬†

Scientists at Washington University School of Medicine in St. Louis have detailed the structured of a molecule that has been implicated in Alzheimer’s disease. Knowing the shape of the molecule – and how that shape may be disrupted by certain genetic mutations – can help in understanding how Alzheimer’s and other neurodegenerative diseases develop and how to prevent and treat them. The idea is that molecule TREM2 involved in cognitive decline – the hallmark of neurodegenerative diseases, including Alzheimer’s – has gained certain mutations that alter the structure of TREM2 are associated with an increased risk of developing late-onset Alzheimer’s, frontal temporal dementia, Parkinson’s disease and sporadic amyotrophic lateral sclerosis (ALS). Other TREM2 mutations are linked Nasu-Hakola disease, a rare inherited condition that causes progressive dementia and death in most patients by age 50. “We don’t know exactly what dysfunctional TREM2 does to contribute to neurodegeneration, but we know inflammation is the common thread in all these conditions,” said senior author Thomas J. Brett, PhD, as assistant professor of medicine. “Our study looked at these mutations in TREM2 and asked what they do to the structure of the protein itself, and how that might impact its function. If we can understand that, we can begin to look for ways to correct it.”

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