Establishing the interchangeability between CSF and PET to identify patients with Alzheimer’s disease pathology

<h3>Objectives</h3> PET tracers represent the gold-standard for indicating the presence of Alzheimer’s disease (AD) pathology, but are costly and not widely accessible. Thus, establishing the interchangeability of CSF and PET for patient identification (PI) may overcome barriers to inequitable access for AD modifying therapies. <h3>Methods</h3> AD Neuroimaging Initiative participants with MCI/AD dementia and available CSF data, amyloid-PET and/or tau-PET scans were included. Agreement between PET and CSF- based PI, the non-inferiority of CSF to amyloid-PET for PI, and clinical/cognitive trajectories were evaluated. <h3>Results</h3> Fujirebio-Lumipulse Aβ42/40 (N=288) and Roche-Elecsys P-tau181/Aβ42 (N=251) CSF-assays ruled-in the same participants as amyloid-PET (Positive Predictive Values (PPV) of 89.58% and 93.53%, respectively) and met non-inferiority criteria. Roche-Elecsys P-tau181/Aβ42 (N=127) ruled-out, but not in, the same participants as neocortical tau-PET (negative predictive value (NPV) 98.08%; PPV=64.00%), although a Youden’s Index-based CSF threshold resulted in &gt;80% positive and negative percent agreements. CSF+/tau-PET− had faster clinical/cognitive decline than CSF−/tau-PET−. CSF achieved 81.33%PPV and 94.23%NPV vs early tau-PET. <h3>Conclusions</h3> CSF assays are non-inferior to Aβ-PET for identifying patients with AD pathology. Alternative thresholds for CSF assays, derived against tau instead of amyloid pathology, may better align with neocortical tau-PET. Further consideration of CSF strategies for tau are warranted. Disclosed at ISPOR-2023.