Abstract
Plasma phosphorylated tau (p-tau) and glial fibrillary acidic protein (GFAP) both reflect early changes in Alzheimer's disease (AD) pathology. Here, we compared the biomarker levels and their association with regional β-amyloid (Aβ) pathology and cognitive performance head-to-head in clinically unimpaired elderly (n = 88) at three levels of APOE4-related genetic risk for sporadic AD (APOE4/4 n = 19, APOE3/4 n = 32 or non-carriers n = 37). Concentrations of plasma p-tau181, p-tau231 and GFAP were measured using Single molecule array (Simoa), regional Aβ deposition with 11C-PiB positron emission tomography (PET), and cognitive performance with a preclinical composite. Significant differences in plasma p-tau181 and p-tau231, but not plasma GFAP concentrations were present between the APOE4 gene doses, explained solely by brain Aβ load. All plasma biomarkers correlated positively with Aβ PET in the total study population. This correlation was driven by APOE3/3 carriers for plasma p-tau markers and APOE4/4 carriers for plasma GFAP. Voxel-wise associations with amyloid-PET revealed different spatial patterns for plasma p-tau markers and plasma GFAP. Only higher plasma GFAP correlated with lower cognitive scores. Our observations suggest that plasma p-tau and plasma GFAP are both early AD markers reflecting different Aβ-related processes.
| Original language | English |
|---|---|
| Article number | 106175 |
| Journal | Neurobiology of Disease |
| Volume | 183 |
| DOIs | |
| Publication status | Published - Jul 2023 |
| MoE publication type | A1 Journal article-refereed |
Funding
This work was supported by the Finnish Governmental Research Funding (VTR) for Turku University Hospital and Academy of Finland (#310962 and #341059). AS was additionally supported by the Emil Aaltonen Foundation, the Paulo Foundation, and the Orion Research Foundation sr. LLE was supported by the Emil Aaltonen foundation, the Juho Vainio foundation and the Paulo Foundation. EP was supported by the Paulo Foundation, the Yrjö Jahnsson Foundation, the Betania Foundation and the Kunnanlääkäri Uulo Arhio Foundation. JOR has received funding from the Academy of Finland (#310962), Sigrid Juselius Foundation and Finnish Governmental Research Funding (VTR) for Turku University Hospital. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018–02532), the European Union's Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809–2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022–0270), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021–00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). KB was supported by the Swedish Research Council (#2017–00915 and #2022–00732), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017–0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019–466-236), and the National Institute of Health (NIH), USA, (grant #1R01AG068398–01). JOR received funding from the Academy of Finland (#310962), the Sigrid Juselius Foundation, and Finnish Governmental Research Funding (VTR).HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. Other authors do not report any conflicts of interest. This work was supported by the Finnish Governmental Research Funding (VTR) for Turku University Hospital and Academy of Finland (#310962 and #341059). AS was additionally supported by the Emil Aaltonen Foundation , the Paulo Foundation , and the Orion Research Foundation sr. LLE was supported by the Emil Aaltonen foundation , the Juho Vainio foundation and the Paulo Foundation . EP was supported by the Paulo Foundation , the Yrjö Jahnsson Foundation , the Betania Foundation and the Kunnanlääkäri Uulo Arhio Foundation. JOR has received funding from the Academy of Finland (#310962), Sigrid Juselius Foundation and Finnish Governmental Research Funding (VTR) for Turku University Hospital. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018–02532), the European Union's Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809–2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022–0270), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021–00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). KB was supported by the Swedish Research Council (#2017–00915 and #2022–00732), the Alzheimer Drug Discovery Foundation (ADDF) , USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017–0243), the Swedish state under the agreement between the Swedish government and the County Councils , the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019–466-236), and the National Institute of Health (NIH) , USA, (grant #1R01AG068398–01). JOR received funding from the Academy of Finland (#310962), the Sigrid Juselius Foundation, and Finnish Governmental Research Funding (VTR).