Columbia University researchers discover new clues to Alzheimer’s origins
A fragile cleanup system sitting on the surface of brain cells may help explain one of Alzheimer’s disease’s oldest mysteries. It may reveal how ordinary tau protein first turns into the twisted filaments tied to memory loss and cognitive decline. That is the central finding from a Columbia University team that traced the earliest stages of tau damage to a neuron-specific protein disposal system called the neuroproteasome. When that system was disrupted, tau rapidly misfolded into paired helical filaments. This is the same broad kind of abnormal structure seen in the brains of people with Alzheimer’s disease. The work points to a possible starting point for tau pathology. Additionally, it connects two of the disease’s biggest risk factors: aging and the APOE4 gene variant. “These prior studies could not capture how tau misfolds in the first place in Alzheimer’s disease but understanding how tau aggregation begins is critical if we want to create therapies that prevent neurodegeneration before it starts,” says the study’s senior author, Kapil Ramachandran, assistant professor of neurological sciences at Columbia University. …
