ApoE4 lowers the ptau217 threshold for tau aggregation and spread in an allele dose-dependent manner
Published in Brain, 2025
This research investigates the mechanism by which the Apolipoprotein E ε4 (ApoE4) allele, the strongest genetic risk factor for sporadic Alzheimer’s disease, accelerates disease progression. The study found that ApoE4 does not alter initial amyloid-related ptau secretion, but instead enhances the spread of fibrillar tau, leading to an earlier transition from amyloidosis to tauopathy at lower levels of plasma ptau217.
These findings have direct implications for clinical practice, suggesting that plasma ptau-based screening approaches and the optimal timing for anti-amyloid treatments may need to be adjusted based on a patient’s ApoE4 genotype.
Recommended citation: Steward, A., Dewenter, A., Hirsch, F., Roemer-Cassiano, S. N., Zhu, Z., Dehsarvi, A., Biel, D., Klonowski, M., Frontzkowski, L., Palleis, C., Gnörich, J., Dichgans, M., Höglinger, G., Brendel, M., & Franzmeier, N. (2025). ApoE4 lowers the ptau217 threshold for tau aggregation and spread in an allele dose-dependent manner. Brain, awaf463. https://doi.org/10.1093/brain/awaf463
Recommended citation: Steward, A., Dewenter, A., Hirsch, F., Roemer-Cassiano, S. N., Zhu, Z., Dehsarvi, A., Biel, D., Klonowski, M., Frontzkowski, L., Palleis, C., Gnörich, J., Dichgans, M., Höglinger, G., Brendel, M., & Franzmeier, N. (2025). ApoE4 lowers the ptau217 threshold for tau aggregation and spread in an allele dose-dependent manner. Brain, awaf463. https://doi.org/10.1093/brain/awaf463
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