Plasma phospho‐tau181 increases with Alzheimer's disease clinical severity and is associated with tau‐ and amyloid‐positron emission tomography
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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.
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Blood measures of p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40 have been shown to change in preclinical AD and can discriminate this state from CU individuals with non-AD pathological changes.
“Indeed, blood measures of p-tau181, p-tau217, p-tau231, glial fibrillary acid protein (GFAP), neurofilament light (NfL) and Aβ42/40 have been shown to change in preclinical AD and can discriminate this state from CU individuals with non-AD pathological changes1,3,6–13.”
From Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease (2022) · cites this paper as [6]
Results §3.2 and §3.5 report that plasma pTau181 was associated with elevated amyloid PET among cognitively unimpaired (CU) participants and had predictive value for elevated amyloid PET. However, Results §3.3 found no difference in mean pTau181 between CU amyloid-positive and amyloid-negative groups. The paper does not establish discrimination from CU individuals with non-AD pathological changes or assess the other biomarkers listed in the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFew blood markers exist for the presymptomatic stage of Alzheimer's disease, though some progress has been reported for blood amyloid-β, tau, and NfL.
“Blood biomarkers for the presymptomatic phase of Alzheimer’s disease are largely lacking, although recent progress in the analysis of amyloid-β, tau, and neurofilament light chain (NfL) in the blood have been reported5–10.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [10]
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References 34 · Cited by 621
- Authors
- Mielke, M. M., Hagen, C. E., Xu, J., Chai, X., Vemuri, P., Lowe, V. J., Airey, D. C., Knopman, D. S., Roberts, R. O., Machulda, M. M., Jack, C. R., Petersen, R. C., & Dage, J. L.
- Affiliations
- Mayo Clinic (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Mielke, Michelle M.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-04-04
- Volume
- 14
- Issue
- 8
- Pages
- 989-997
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6097897
- OpenAlex
- W2795642715
- Cited by
- 621
- References
- 34
- Citations by year
- 2026: 47 · 2025: 84 · 2024: 106 · 2023: 73 · 2022: 93 · 2021: 94 · 2020: 82 · 2019: 33 · 2018: 8
- FWCI
- 42.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (W81XWH-15-1)
- GE Healthcare
- Avid Radiopharmaceuticals
- National Institutes of Health (R01 AG011378, U01 HL096917, U01 AG024904, RO1 AG041851, R01 AG037551, R01 AG043392, U01 AG006786, P50 AG016574)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Magnetic Resonance Imaging, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction
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