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Head-to-head comparison between plasma p-tau217 and flortaucipir-PET in amyloid-positive patients with cognitive impairment.
Mundada, Nidhi S; Rojas, Julio C; Vandevrede, Lawren; Thijssen, Elisabeth H; Iaccarino, Leonardo; Okoye, Obiora C; Shankar, Ranjani; Soleimani-Meigooni, David N; Lago, Argentina L; Miller, Bruce L; Teunissen, Charlotte E; Heuer, Hillary; Rosen, Howie J; Dage, Jeffrey L; Jagust, William J; Rabinovici, Gil D; Boxer, Adam L; La Joie, Renaud.
Affiliation
  • Mundada NS; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Rojas JC; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Vandevrede L; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Thijssen EH; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Iaccarino L; Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
  • Okoye OC; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Shankar R; Eli Lilly and Company, Indianapolis, IN, USA.
  • Soleimani-Meigooni DN; Global Brain Health Institute, San Francisco, CA, USA.
  • Lago AL; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Miller BL; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Teunissen CE; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Heuer H; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Rosen HJ; Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
  • Dage JL; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Jagust WJ; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Rabinovici GD; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Boxer AL; University of California, Berkeley, Berkeley, CA, USA.
  • La Joie R; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Alzheimers Res Ther ; 15(1): 157, 2023 09 22.
Article in En | MEDLINE | ID: mdl-37740209
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 (11C-PIB), tau-PET (18F-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease / Cognitive Dysfunction Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Alzheimers Res Ther Year: 2023 Document type: Article Affiliation country: Estados Unidos Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease / Cognitive Dysfunction Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Alzheimers Res Ther Year: 2023 Document type: Article Affiliation country: Estados Unidos Country of publication: Reino Unido