Predictors of sex-specific resistance to caTAUstrophe

ABSTRACT INTRODUCTION As β-amyloid(Aβ) 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 Aβ+ men and women. METHODS Employing data from 872 Aβ+ older adults(N Test =579) across three cohorts, we estimated resistance, defined as the deviation from participant’s expected level of neocortical tau. Models predicting the expected tau levels were trained separately in females(N Train =172) and males(N Train =121) experiencing ‘typical’ tau progression to assess sex-specific resistance. RESULTS Relative feature importance in female-only and male-only expectation models differed in 97.7% of variables(p[FDR]