Associations between [¹⁸F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample.

Abstract

To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([¹⁸F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ₄₂, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. [¹⁸F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [¹⁸F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau (<i>r</i> = 0.75 vs 0.57 for t-tau and -0.49 for Aβ₄₂). When restricted to Aβ-positive patients with AD, [¹⁸F]AV1451 SUVR correlated modestly with p-tau and t-tau (both <i>r</i> = 0.46) but not Aβ₄₂ (<i>r</i> = 0.02). On voxelwise analysis, [¹⁸F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [¹⁸F]AV1451-PET, but not CSF biomarkers. [¹⁸F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [¹⁸F]AV1451 distinguish AD from non-AD conditions.