4.7 Article

Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau

Journal

ALZHEIMERS & DEMENTIA
Volume 18, Issue 8, Pages 1523-1536

Publisher

WILEY
DOI: 10.1002/alz.12508

Keywords

Alzheimer's Disease; P-tau; Plasma biomarkers; Network analysis; Neuropsychology

Funding

  1. National Institutes of Health [P30AG013846, K23 NS102399, R01 HL141774-02, R01 OH011511-01, R01 HD090191, R01AG062348, U01 NS093334, RF1 AG054156, R01-1AG070883-01, NIH R01 PAR-19-070, P30AG13846, PAR-19070, U01-AG068057, R56-AG069130]
  2. Department of Veterans' Affairs [I01-CX001038, 1I01BX004613, BX002466]
  3. National Center for Advancing Translational Sciences, National Institutes of Health, through BU-CTSI Grant [1UL1TR001430]
  4. Swedish Research Council [2018-02532, 2017-00915]
  5. European Research Council [681712]
  6. Swedish State Support for Clinical Research [ALFGBG-720931]
  7. Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-201809-2016615]
  8. Alzheimer's Association [ADSF-21-831376-C, ADSF-21831381-C, ADSF-21-831377-C]
  9. Olav Thon Foundation
  10. Erling-Persson Family Foundation
  11. Stiftelsen for Gamla Tjanarinnor
  12. Hjarnfonden, Sweden [FO2019-0228, FO2017-0243]
  13. European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]
  14. UK Dementia Research Institute at UCL
  15. Swedish Alzheimer Foundation [AF-742881]
  16. Swedish government [ALFGBG-715986]
  17. County Councils, the ALF-agreement [ALFGBG-715986]
  18. European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
  19. National Institute of Health (NIH), USA [1R01AG068398-01]
  20. Brightfocus Foundation [A2020812F]
  21. Swedish Alzheimer Foundation (Alzheimerfonden) [AF-930627]
  22. Swedish Brain Foundation (Hjarnfonden) [FO2020-0240]
  23. Swedish Parkinson Foundation (Parkinsonfonden)
  24. Swedish Dementia Foundation (Demensforbundet)
  25. Agneta Prytz-Folkes & Gosta Folkes Foundation [2020-00124]
  26. Aina (Ann) Wallstroms and Mary-Ann Sjobloms Foundation
  27. Anna Lisa andBrother Bjornsson's Foundation
  28. Gamla Tjanarinnor
  29. Gun and Bertil Stohnes Foundation
  30. US Department of Veterans Affairs [IK2 CX002065]
  31. NIH/NIA [AG033040, AG049899, AG049810, AG054156, AG055337, AG016495, AG062109, AG059011, AG061340, AG063635, AG068753]
  32. Alzheimer's Drug Discovery Foundation [VMF-14-318524]
  33. Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award [I01-CX001038]
  34. National Institute of Aging [RF1AG054156, RF1AG057768, U19AG068753, U54NS115266, RF1 AG057902]
  35. National Institute of Neurological Disorders and Stroke [U54NS115266]
  36. Department of Defense [AZ170038, CDMRP/GWIRP GW180103, W81XWH1810580]
  37. NINDS/NIA [R01NS11965, R01AG062624, U01NS093334, P30-AG13846]
  38. Boston University Alzheimer's Disease Center [AG013846]
  39. The National Institutes of Health [U19AG068753, U54NS115266, U01NS093334, R01-AG069453, R01 AG058822, R01 AG062348, R01AG029672, U01AG032984, R01AG048927, RF1AG057902, R01AG061028, R01AG062602, U19AG06875, U01NS086659-01, RF1AG05416, K23NS102399]
  40. AD Strategic Fund
  41. U.S. Department of Defense (DOD) [W81XWH1810580] Funding Source: U.S. Department of Defense (DOD)
  42. MRC [UKDRI-1003] Funding Source: UKRI

Ask authors/readers for more resources

The study found that plasma p-tau(181) is effective in detecting AD dementia and supports the use of blood-based biomarkers for optimal disease detection. Plasma NfL also showed potential in discriminating diagnostic groups, while p-tau(181) had a direct association with cognitive diagnosis.
Introduction We examined the ability of plasma hyperphosphorylated tau (p-tau)(181) to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL). Methods Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables. Results Plasma p-tau(181) discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau(181) had a direct association with cognitive diagnosis in a bootstrapped GGM. Discussion These results support plasma p-tau(181) for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.

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