This is a vitally important paper that provides further evidence for a "silent period" lasting many decades before AD is clinically diagnosed. The authors found abnormally hyperphosphorylated tau in subcortical regions in people between ages four and 29. The existence of this long "silent" period provides a window of opportunity for earlier detection than is usually considered, and earliest intervention. On the other hand, as the authors indicate, is this evidence of a dynamic process in which these changes are transient cycling among cells?

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