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Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads

Salvadó, Gemma LU ; Ossenkoppele, Rik LU ; Ashton, Nicholas J. ; Beach, Thomas G. ; Serrano, Geidy E. ; Reiman, Eric M. ; Zetterberg, Henrik LU ; Mattsson-Carlgren, Niklas LU orcid ; Janelidze, Shorena LU and Blennow, Kaj LU , et al. (2023) In EMBO Molecular Medicine 15(5).
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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, co-pathologies, head-to-head, neuropathology, p-tau species
in
EMBO Molecular Medicine
volume
15
issue
5
article number
e17123
publisher
Wiley-Blackwell
external identifiers
  • pmid:36912178
  • scopus:85150619459
ISSN
1757-4676
DOI
10.15252/emmm.202217123
language
English
LU publication?
yes
id
d9bf2756-60df-44d6-9340-82329aae6341
date added to LUP
2023-05-29 14:05:13
date last changed
2024-04-05 19:59:58
@article{d9bf2756-60df-44d6-9340-82329aae6341,
  abstract     = {{<p>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 (ρ<sub>Aβ42/40</sub>[95%CI] = −0.53[−0.65, −0.35], ρ<sub>p-tau231</sub>[95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρ<sub>GFAP</sub>[95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (ρ<sub>p-tau217</sub>[95%CI] = 0.40[0.21, 0.56], ρ<sub>p-tau181</sub>[95%CI] = 0.36[0.15, 0.50]) and tangles (ρ<sub>p-tau217</sub>[95%CI] = 0.52[0.34, 0.66]; ρ<sub>p-tau181</sub>[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 (R<sup>2</sup> = 0.55), while p-tau217 alone was optimal for predicting tangle load (R<sup>2</sup> = 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.</p>}},
  author       = {{Salvadó, Gemma and Ossenkoppele, Rik and Ashton, Nicholas J. and Beach, Thomas G. and Serrano, Geidy E. and Reiman, Eric M. and Zetterberg, Henrik and Mattsson-Carlgren, Niklas and Janelidze, Shorena and Blennow, Kaj and Hansson, Oskar}},
  issn         = {{1757-4676}},
  keywords     = {{Alzheimer's disease; co-pathologies; head-to-head; neuropathology; p-tau species}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads}},
  url          = {{http://dx.doi.org/10.15252/emmm.202217123}},
  doi          = {{10.15252/emmm.202217123}},
  volume       = {{15}},
  year         = {{2023}},
}