The three most harmful forms of metabolic waste in the aging brain are amyloid-β, hyperphosphorylated tau, and α-synuclein, all of which precipitate into solid deposits with a complex halo of surrounding biochemistry that damages and ultimately kills cells. They contribute to various age-related neurodegenerative conditions that are classified as amyloidosis, tauopathy, and synucleinopathy, respectively. Looking at just one of these forms of waste in isolation misses the real story, however. An aging brain has some of each, and it is apparent from the study of Alzheimer’s disease that amyloid-β and tau interact to produce greater harm together than either does on its own. So should we be surprised to find evidence that tau and α-synuclein also have synergies in well known synucleinopathies such as Parkinson’s disease? Perhaps not.
This sort of finding favors approaches to clearance of metabolic waste that tackle all of it at once, not just selective types. The most expensive, and so far failed, immunotherapies for Alzheimer’s disease, for example, focus specifically on amyloid-β, or more recently specifically on tau. The more that we see interaction between these forms of damaged protein in the brain, the more we should favor methodologies for clearance of
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