TauImmunotherapyModulatesBothPathologicalTauand UpstreamAmyloidPathologyinanAlzheimer'sDisease MouseModel

InAlzheimer’sdisease(AD),thepathologicalaccumulationoftauappearstobeadownstreameffectofamyloidprotein(A).However, therelationshipbetweenthesetwoproteinsandmemorylossisunclear.Inthisstudy,weevaluatedthespecificremovalofpathological tauoligomersinagedTg2576micebypassiveimmunotherapyusingtauoligomer-specificmonoclonalantibody.Removaloftauoligomers reversed memory deficits and accelerated plaque deposition in the brain. Surprisingly, A*56 levels decreased, suggesting a link between tau and A oligomers in the promotion of cognitive decline. The results suggest that tau oligomerization is not only a consequence of A pathology but also a critical mediator of the toxic effects observed afterward in AD. Overall, these findings support the potentialoftauoligomersasatherapeutictargetforAD.