Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads
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, Aβ4...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-05-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202217123 |
| _version_ | 1797283746700853248 |
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| author | Gemma Salvadó Rik Ossenkoppele Nicholas J Ashton Thomas G Beach Geidy E Serrano Eric M Reiman Henrik Zetterberg Niklas Mattsson‐Carlgren Shorena Janelidze Kaj Blennow Oskar Hansson |
| author_facet | Gemma Salvadó Rik Ossenkoppele Nicholas J Ashton Thomas G Beach Geidy E Serrano Eric M Reiman Henrik Zetterberg Niklas Mattsson‐Carlgren Shorena Janelidze Kaj Blennow Oskar Hansson |
| author_sort | Gemma Salvadó |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:35:20Z |
| format | Article |
| id | doaj.art-adc3e327988745318065d88c1f77d745 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:35:20Z |
| publishDate | 2023-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-adc3e327988745318065d88c1f77d7452024-03-02T16:53:29ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-05-01155n/an/a10.15252/emmm.202217123Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loadsGemma Salvadó0Rik Ossenkoppele1Nicholas J Ashton2Thomas G Beach3Geidy E Serrano4Eric M Reiman5Henrik Zetterberg6Niklas Mattsson‐Carlgren7Shorena Janelidze8Kaj Blennow9Oskar Hansson10Clinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University Lund SwedenClinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University Lund SwedenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy University of Gothenburg Gothenburg SwedenBanner Sun Health Research Institute Sun City AZ USABanner Sun Health Research Institute Sun City AZ USABanner Alzheimer's Institute Arizona State University and University of Arizona Phoenix AZ USADepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy University of Gothenburg Gothenburg SwedenClinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University Lund SwedenClinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University Lund SwedenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy University of Gothenburg Gothenburg SwedenClinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University Lund SwedenAbstract 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.https://doi.org/10.15252/emmm.202217123Alzheimer's diseaseco‐pathologieshead‐to‐headneuropathologyp‐tau species |
| spellingShingle | Gemma Salvadó Rik Ossenkoppele Nicholas J Ashton Thomas G Beach Geidy E Serrano Eric M Reiman Henrik Zetterberg Niklas Mattsson‐Carlgren Shorena Janelidze Kaj Blennow Oskar Hansson Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads EMBO Molecular Medicine Alzheimer's disease co‐pathologies head‐to‐head neuropathology p‐tau species |
| title | Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| title_full | Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| title_fullStr | Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| title_full_unstemmed | Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| title_short | Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| title_sort | specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads |
| topic | Alzheimer's disease co‐pathologies head‐to‐head neuropathology p‐tau species |
| url | https://doi.org/10.15252/emmm.202217123 |
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