White matter microstructural degeneration is spatiotemporally correlated with tau accumulation in Autosomal Dominant Alzheimer disease

While global white matter differences are detected between mutation-carriers and non-carriers close to symptom onset, tracts that are adjacent to regions of significant tau accumulation show microstructural abnormality much earlier. This confirms that ADAD white matter decline does not occur uniformly across the brain, and may suggest a spatial correlation with tau. The timing of tract-specific decline may also support that white matter damage occurs downstream of tau accumulation and spread. Given that white matter is critically important for transduction and integration of signals across disparate brain regions, the continued characterization of tau and white matter progression may provide important insight into the mechanism through which tau drives cognitive symptom onset in ADAD.