Journal Article

Head-to-head comparison between plasma p-tau217 and flortaucipir-PET in amyloid-positive patients with cognitive impairment

Mundada, Nidhi S., Heuer, Hillary, Jagust, William J., Thijssen, Elisabeth H., Rabinovici, Gil D., Teunissen, Charlotte E., Shankar, Ranjani, Dage, Jeffrey L., Rosen, Howie J., La Joie, Renaud, Okoye, Obiora C., Iaccarino, Leonardo, Vandevrede, Lawren, Rojas, Julio C., Lago, Argentina L., Miller, Bruce L., Soleimani-Meigooni, David N., Boxer, Adam L.

2023

Overview

Background Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer’s disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables. Methods We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET ( 11 C-PIB), tau-PET ( 18 F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline ( n  = 85) and follow-up visits ( n  = 28; 1.5 ± 0.7 years). Results Plasma p-tau217 and cortical FTP-SUVR were correlated ( r  = 0.61, p  < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR ( r  = 0.26, p  = 0.02), but not with p-tau217 ( r  = 0.10, p  = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model. Conclusion Plasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Aged / Alzheimer Disease - diagnostic imaging / Alzheimer's disease / Amyloidogenic Proteins / Biological markers / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cognition disorders / Cognitive ability / Cognitive Dysfunction - diagnostic imaging / Contrast media / Dementia / Diagnosis / Disease / Female / Geriatric Psychiatry / Geriatrics/Gerontology / Health aspects / Humans / Independent variables / Male / MCI (mild cognitive impairment) / Measurement / Middle Aged / Mild cognitive impairment / MRI / Neurological research / Neurology / Neurosciences / Patients / PET imaging / Plasma / Plasma biomarkers / Retrospective Studies / Tau proteins / Tau-PET