TitleAssociations between [F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample.
Publication TypeJournal Article
Year of Publication2018
AuthorsLa Joie R, Bejanin A, Fagan AM, Ayakta N, Baker SL, Bourakova V, Boxer AL, Cha J, Karydas A, Jerome G, Maass A, Mensing A, Miller ZA, O'Neil JP, Pham J, Rosen HJ, Tsai R, Visani AV, Miller BL, Jagust WJ, Rabinovici GD
Date Published2018 Jan 23

OBJECTIVE: To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample.

METHODS: Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ, 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.

RESULTS: [F]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 [F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau ( = 0.75 vs 0.57 for t-tau and -0.49 for Aβ). When restricted to Aβ-positive patients with AD, [F]AV1451 SUVR correlated modestly with p-tau and t-tau (both = 0.46) but not Aβ ( = 0.02). On voxelwise analysis, [F]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 [F]AV1451-PET, but not CSF biomarkers.

CONCLUSION: [F]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.

CLASSIFICATION OF EVIDENCE: 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 [F]AV1451 distinguish AD from non-AD conditions.

Alternate JournalNeurology
PubMed ID29282337
PubMed Central IDPMC5798657
Grant ListP50 AG023501 / AG / NIA NIH HHS / United States
P01 AG003991 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
P01 AG026276 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
U54 NS092089 / NS / NINDS NIH HHS / United States