The primary objective of this proposal is to address the major unmet need for a simple, convenient and readily accessible blood test that can predict brain AD pathology. The intended context of use (COU) is a diagnostic plasma biomarker test that identifies people with probable AD pathology among those experiencing unexplained mild cognitive impairment (MCI) or dementia. There are two aims: (i) Clinical validation of the plasma Aβ42/Aβ40 test in a large scale, real-life independent at-risk cohort, and (ii) Assess the impact of blood sample collection and handling parameters on plasma Aβ42/Aβ40 quantitation. Earlier detection has the potential to significantly improve clinical outcomes for at-risk individuals. Further, a blood test has the potential to accelerate efficient and eligible participant’s enrollment into AD drug trials which can provide them with earlier access to novel disease-modifying therapies once they become available.