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. 2018 Aug;14(8):989-997.
doi: 10.1016/j.jalz.2018.02.013. Epub 2018 Apr 5.

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography

Michelle M Mielke  1 , Clinton E Hagen  2 , Jing Xu  3 , Xiyun Chai  3 , Prashanthi Vemuri  4 , Val J Lowe  4 , David C Airey  3 , David S Knopman  5 , Rosebud O Roberts  6 , Mary M Machulda  7 , Clifford R Jack Jr  4 , Ronald C Petersen  6 , Jeffrey L Dage  3
Affiliations

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography

Michelle M Mielke et al. Alzheimers Dement. 2018 Aug.

Abstract

Introduction: We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ.

Methods: Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181.

Results: Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE).

Discussion: Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ.

Keywords: Alzheimer's disease; Amyloid PET; Plasma phosphorylated tau; Plasma tau; Predicting brain amyloid; Tau PET.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Mielke served as a consultant to Eli Lilly and Lysosomal Therapeutics, Inc., and receives research support from the National Institutes of Health (R01 AG49704, P50 AG44170, U01 AG06786 RF1 AG55151), Department of Defense (W81XWH-15-1), and unrestricted research grants from Biogen, Roche, and Lundbeck. Mr. Hagen has no disclosures. Drs. Xu, Chai, Airey and Dage are employees of Eli Lilly. Dr Lowe consults for Bayer Schering Pharma, Piramal Life Sciences and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals and the NIH (NIA, NCI). Drs. Machulda receives research support from the National Institutes of Health (U01 AG006786). Dr. Roberts receives research support from the National Institutes of Health (U01 AG006786) and an unrestricted research grant from F. Hoffman-La Roche. Dr. Knopman served as Deputy Editor for Neurology®; serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by TauRx Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer’s Disease Cooperative Study; and receives research support from the NIH (R01 AG011378, P50 AG016574, U01 AG006786, AG029550, AG032306, and U01 HL096917). Dr. Jack has provided consulting services for Eli Lilly. He receives research funding from the National Institutes of Health (R01 AG011378, U01 HL096917, U01 AG024904, RO1 AG041851, R01 AG037551, R01 AG043392, and U01 AG006786), and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. Dr. Petersen serves on scientific advisory boards for Roche, Inc., Merck, Inc., Biogen, Inc., and Genentech, Inc.; receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the National Institutes of Health (P50 AG016574, U01 AG006786, U01 AG024904, and R01 AG011378).

Figures

Fig. 1
Fig. 1
(A) Mean (SD) plasma phospho-tau 181, and (B) mean (SD) total tau by clinical diagnosis and elevated Aβ PET. Abbreviations: AD, Alzheimer’s disease dementia; CU, cognitively unimpaired; MCI, mild cognitive impairment. For illustrative purposes only, the following outliers were not included: (A) 1 CU at 75.7 pg/ml and 2 MCI at 62.4 and 93.3 pg/ml; (B) none. *P < .05; **P < .01
See this image and copyright information in PMC

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