Brandon Frank1,2, Madeline Ally1, Bailee Brekke1, Henrik Zetterberg3,4,5,6, Kaj Blennow5,6, Michael A Sugarman1,2, Nicholas J Ashton5,6, Thomas K Karikari5,6, Yorghos Tripodis1,7, Brett Martin1,8, Joseph N Palmisano1,8, Eric G Steinberg1, Irene Simkina9, Katherine W Turk1,10,11, Andrew E Budson1,10,11, Maureen K O'Connor1,2, Rhoda Au1,10,12,13,14, Lee E Goldstein1,15,16,17, Gyungah R Jun9, Neil W Kowall1,10,15,11, Thor D Stein1,2,15,11, Ann C McKee1,2,10,15,11, Ronald Killiany1,10,12,18, Wei Qiao Qiu1,19,20, Robert A Stern1,10,12,21, Jesse Mez1,10,13, Michael L Alosco1,10. 1. Boston University Alzheimer's Disease Center and CTE Center, Boston University School of Medicine, Boston, Massachusetts, USA. 2. U.S. Department of Veteran Affairs, VA Bedford Healthcare System, Bedford, Massachusetts, USA. 3. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 4. UK Dementia Research Institute at UCL, London, UK. 5. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 6. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 7. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. 8. Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts, USA. 9. Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. 10. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. 11. U.S. Department of Veteran Affairs, VA Boston Healthcare System, Jamaica Plain, Massachusetts, USA. 12. Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, Massachusetts, USA. 13. Framingham Heart Study, Boston University School of Medicine, Boston, Massachusetts, USA. 14. Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA. 15. Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. 16. Departments of Psychiatry and Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA. 17. Departments of Biomedical, Electrical & Computer Engineering, Boston University College of Engineering, Boston, Massachusetts, USA. 18. Center for Biomedical Imaging, Boston University School of Medicine, Boston, Massachusetts, USA. 19. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA. 20. Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA. 21. Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts, USA.
Abstract
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-tau181 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-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM. DISCUSSION: These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.
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-tau181 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-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM. DISCUSSION: These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.
Authors: Sid E O'Bryant; Stephen C Waring; C Munro Cullum; James Hall; Laura Lacritz; Paul J Massman; Philip J Lupo; Joan S Reisch; Rachelle Doody Journal: Arch Neurol Date: 2008-08
Authors: Michael A Sugarman; Henrik Zetterberg; Kaj Blennow; Yorghos Tripodis; Ann C McKee; Thor D Stein; Brett Martin; Joseph N Palmisano; Eric G Steinberg; Irene Simkin; Andrew E Budson; Ronald Killiany; Maureen K O'Connor; Rhoda Au; Wendy Wei Qiao Qiu; Lee E Goldstein; Neil W Kowall; Jesse Mez; Robert A Stern; Michael L Alosco Journal: Neurobiol Aging Date: 2020-05-29 Impact factor: 4.673
Authors: Nicholas J Ashton; Tharick A Pascoal; Pedro Rosa-Neto; Kaj Blennow; Thomas K Karikari; Andréa L Benedet; Juan Lantero-Rodriguez; Gunnar Brinkmalm; Anniina Snellman; Michael Schöll; Claire Troakes; Abdul Hye; Serge Gauthier; Eugeen Vanmechelen; Henrik Zetterberg Journal: Acta Neuropathol Date: 2021-02-14 Impact factor: 17.088
Authors: Ignacio Illán-Gala; Alberto Lleo; Anna Karydas; Adam M Staffaroni; Henrik Zetterberg; Rajeev Sivasankaran; Lea T Grinberg; Salvatore Spina; Joel H Kramer; Eliana M Ramos; Giovanni Coppola; Renaud La Joie; Gil D Rabinovici; David C Perry; Maria Luisa Gorno-Tempini; William W Seeley; Bruce L Miller; Howard J Rosen; Kaj Blennow; Adam L Boxer; Julio C Rojas Journal: Neurology Date: 2020-11-16 Impact factor: 11.800