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bioRxiv · 10.1101/2020.05.18.103226

Time between milestone events in the Alzheimer's disease amyloid cascade

Insel, P.·Donohue, M.·Berron, D.·Hansson, O.·Mattsson-Carlgren, N.
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Abstract

ObjectiveEstimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimers disease. MethodsIn a cohort of 336 older adults, ranging in cognitive functioning, we estimated the time of initial changes of A{beta}, tau, and decreases in cognition with respect to the time of A{beta}-positivity. ResultsSmall effect sizes of change in CSF A{beta}42 and regional A{beta} PET were estimated to occur several decades before A{beta}-positivity. Increases in CSF tau occurred 11-12 years before A{beta}-positivity. Temporoparietal tau PET showed increases 4-5 years before A{beta}-positivity. Subtle cognitive dysfunction was observed 7-9 years before A{beta}-positivity. ConclusionsIncreases in tau and cognitive dysfunction occur years before the presence of significant A{beta}. Explicit estimates of the time for these events provide a clearer picture of the time course of the amyloid cascade and identify potential windows for specific treatments.

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Insel, P., Donohue, M., Berron, D., Hansson, O., Mattsson-Carlgren, N.. 2020-05-21. Time between milestone events in the Alzheimer's disease amyloid cascade. https://doi.org/10.1101/2020.05.18.103226

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