Objective: Substantial research indicates that fluid and crystallized abilities are highly correlated throughout the adult lifespan. However, recent proposals suggest that a large discrepancy between these two abilities, defined as crystallized performance minus fluid performance, indicates heightened risk for Alzheimer’s disease (AD). Method: In 266 cognitively healthy older adults, the present study tested linear and quadratic relationships between an ability discrepancy score and early AD neuropathology indexed via in vivo measures of beta-amyloid deposition and cortical thickness in AD-vulnerable regions. We also tested the extent that alternative forms of this ability discrepancy measure (e.g., subdomain discrepancies, verbal-visual discrepancies) and an episodic memory composite might also be sensitive markers of early AD pathology. Results: An overall ability discrepancy was linearly and positively correlated with betaamyloid. A quadratic relationship was found between the overall ability discrepancy score and cortical thickness such that a small positive correlation was found at lower discrepancy levels (fluid > crystallized), but at higher discrepancy (crystallized > fluid) levels a negative relationship was found (i.e., an inverted-U pattern). Similar patterns were found across each subdomain of cognition, but the effects were weaker than the overall ability discrepancy score. Importantly, inclusion of episodic memory (the gold standard) did not alter any of the effects, suggesting that an ability discrepancy confers unique predictiveness of AD biomarkers. Conclusions: These findings replicate previous findings and increase the confidence in their usefulness to predict AD biomarkers. Longitudinal validation is needed to clearly relate an ability discrepancy to specific stages of preclinical AD. Public Significance Statement: Without a cure for Alzheimer’s disease or related dementias, lifestyle modifications for older adults at risk for developing are the only option to prevent or delay these diseases. The present study provided further validation for an inexpensive and non-invasive cognitive measure that might help detect risk for dementia by showing the relationship with this measure and brain markers of Alzheimer’s disease. This measure should serve as a proxy for longitudinal cognitive change and provides the foundation for creating a standardized method that can be implemented in memory clinics.