Predictors of sex-specific resistance to caTAUstrophe

INTRODUCTIONAs {beta}-amyloid(A{beta}) accumulates, tau pathology spreads beyond medial temporal(MTL) regions into the neocortex, though some older adults resist this progression, or caTAUstrophe. Given previous evidence of higher tau levels in women, we tested whether tau resistance presents differently in A{beta}+ men and women. METHODSEmploying data from 872 A{beta}+ older adults(NTest=579) across three cohorts, we estimated resistance, defined as the deviation from participants expected level of neocortical tau. Models predicting the expected tau levels were trained separately in females(NTrain=172) and males(NTrain=121) experiencing typical tau progression to assess sex-specific resistance. RESULTSRelative feature importance in female-only and male-only expectation models differed in 97.7% of variables(p[FDR]<0.001). Moreover, age and A{beta} burden predicted male resistance, while CDR, latent PACC, and adjusted hippocampal volume were predictors for both sexes. DISCUSSIONOur study highlights the impact of sex-specific characteristics in the prediction of neocortical tau resistance. Understanding sex-specific resistance pathways informs targeted Alzheimers interventions.