Salvadó, G;
Ossenkoppele, R;
Ashton, NJ;
Beach, TG;
Serrano, GE;
Reiman, EM;
Zetterberg, H;
... Hansson, O; + view all
(2023)
Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads.
EMBO Molecular Medicine
, Article e2463. 10.15252/emmm.202217123.
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Abstract
Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To investigate and compare independent associations between multiple plasma biomarkers (p-tau181, p-tau217, p-tau231, Aβ42/40, GFAP, and NfL) and neuropathologic measures of amyloid and tau, we included 105 participants from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with antemortem plasma samples and a postmortem neuropathological exam, 48 of whom had longitudinal p-tau217 and p-tau181. When simultaneously including plaque and tangle loads, the Aβ42/40 ratio and p-tau231 were only associated with plaques (ρAβ42/40[95%CI] = −0.53[−0.65, −0.35], ρp-tau231[95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρGFAP[95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (ρp-tau217[95%CI] = 0.40[0.21, 0.56], ρp-tau181[95%CI] = 0.36[0.15, 0.50]) and tangles (ρp-tau217[95%CI] = 0.52[0.34, 0.66]; ρp-tau181[95%CI] = 0.36[0.17, 0.52]). A model combining p-tau217 and the Aβ42/40 ratio showed the highest accuracy for predicting the presence of Alzheimer's disease neuropathological change (ADNC, AUC[95%CI] = 0.89[0.82, 0.96]) and plaque load (R2 = 0.55), while p-tau217 alone was optimal for predicting tangle load (R2 = 0.45). Our results suggest that high-performing assays of plasma p-tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.
| Type: | Article |
|---|---|
| Title: | Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/emmm.202217123 |
| Publisher version: | https://doi.org/10.15252/emmm.202217123 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Alzheimer's disease, co-pathologies, head-to-head, neuropathology, p-tau species |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10167978 |
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