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A comparison of p-tau assays for the specificity to detect tau changes in Alzheimer's disease

Janelidze, Shorena LU ; Ashton, Nicholas J. ; Orduña Dolado, Anna LU ; Nordström, Ulrika LU ; Bali, Divya LU ; Forsberg, Karin M.E. ; Keskin, Isil ; Mastrangelo, Andrea ; Vacchiano, Veria and Liguori, Rocco , et al. (2025) In Alzheimer's and Dementia 21(4).
Abstract

INTRODUCTION: We evaluated differences in p-tau levels between Alzheimer's disease (AD), a condition with brain-specific changes in p-tau, and amyotrophic lateral sclerosis (ALS), a condition associated with increases in peripheral p-tau levels. METHODS: Cerebrospinal fluid and plasma from 668 participants were analyzed using immunoassays specific for the low-molecular-weight (LMW) tau isoforms present in the brain (i.e., p-tau217Lilly, p-tau181Lilly) and those that detect both LMW- and high-molecular-weight (HMW) tau expressed in the peripheral nervous system (i.e., p-tau217AlzPath, p-tau181UGOT). RESULTS: Increases in plasma p-tau in ALS versus controls were significantly smaller for the... (More)

INTRODUCTION: We evaluated differences in p-tau levels between Alzheimer's disease (AD), a condition with brain-specific changes in p-tau, and amyotrophic lateral sclerosis (ALS), a condition associated with increases in peripheral p-tau levels. METHODS: Cerebrospinal fluid and plasma from 668 participants were analyzed using immunoassays specific for the low-molecular-weight (LMW) tau isoforms present in the brain (i.e., p-tau217Lilly, p-tau181Lilly) and those that detect both LMW- and high-molecular-weight (HMW) tau expressed in the peripheral nervous system (i.e., p-tau217AlzPath, p-tau181UGOT). RESULTS: Increases in plasma p-tau in ALS versus controls were significantly smaller for the LMW-specific p-tau assays (15.9%–20.5%) compared with non-specific assays (92.0%–121.3%). The LMW-specific p-tau assays showed significantly larger plasma p-tau increases in AD versus ALS, discriminating AD from ALS with areas under the curve (AUCs; 0.890.93) higher than the AUCs of the non-specific assays (0.54–0.74). DISCUSSION: LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy are frequent. Highlights: Increases in plasma phosphorylated tau (p-tau) in amyotrophic lateral sclerosis (ALS) versus controls were significantly smaller for low-molecular-weight (LMW)–specific p-tau assays (i.e., p-tau217Lilly, p-tau181Lilly) compared with p-tau assays that also detect high-molecular-weight (HMW) assays (i.e., p-tau217AlzPath, p-tau181UGOT). The LMW-specific p-tau assays showed significantly larger increases in plasma p-tau in AD versus ALS compared with the non-specific assays. The LMW-specific p-tau assays discriminated AD from ALS with higher precision, showing significantly better performance than the non-specific assays. LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy (such as ALS) are frequent.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyotrophic lateral sclerosis, biomarker, blood, low-molecular-weight tau, p-tau
in
Alzheimer's and Dementia
volume
21
issue
4
article number
e70208
publisher
Wiley
external identifiers
  • pmid:40289884
  • scopus:105004248623
ISSN
1552-5260
DOI
10.1002/alz.70208
language
English
LU publication?
yes
id
eff64cfd-21bf-4219-9d4a-e1799fb05c8b
date added to LUP
2025-08-12 15:15:03
date last changed
2025-08-13 03:00:03
@article{eff64cfd-21bf-4219-9d4a-e1799fb05c8b,
  abstract     = {{<p>INTRODUCTION: We evaluated differences in p-tau levels between Alzheimer's disease (AD), a condition with brain-specific changes in p-tau, and amyotrophic lateral sclerosis (ALS), a condition associated with increases in peripheral p-tau levels. METHODS: Cerebrospinal fluid and plasma from 668 participants were analyzed using immunoassays specific for the low-molecular-weight (LMW) tau isoforms present in the brain (i.e., p-tau217<sub>Lilly</sub>, p-tau181<sub>Lilly</sub>) and those that detect both LMW- and high-molecular-weight (HMW) tau expressed in the peripheral nervous system (i.e., p-tau217<sub>AlzPath</sub>, p-tau181<sub>UGOT</sub>). RESULTS: Increases in plasma p-tau in ALS versus controls were significantly smaller for the LMW-specific p-tau assays (15.9%–20.5%) compared with non-specific assays (92.0%–121.3%). The LMW-specific p-tau assays showed significantly larger plasma p-tau increases in AD versus ALS, discriminating AD from ALS with areas under the curve (AUCs; 0.890.93) higher than the AUCs of the non-specific assays (0.54–0.74). DISCUSSION: LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy are frequent. Highlights: Increases in plasma phosphorylated tau (p-tau) in amyotrophic lateral sclerosis (ALS) versus controls were significantly smaller for low-molecular-weight (LMW)–specific p-tau assays (i.e., p-tau217Lilly, p-tau181Lilly) compared with p-tau assays that also detect high-molecular-weight (HMW) assays (i.e., p-tau217AlzPath, p-tau181UGOT). The LMW-specific p-tau assays showed significantly larger increases in plasma p-tau in AD versus ALS compared with the non-specific assays. The LMW-specific p-tau assays discriminated AD from ALS with higher precision, showing significantly better performance than the non-specific assays. LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy (such as ALS) are frequent.</p>}},
  author       = {{Janelidze, Shorena and Ashton, Nicholas J. and Orduña Dolado, Anna and Nordström, Ulrika and Bali, Divya and Forsberg, Karin M.E. and Keskin, Isil and Mastrangelo, Andrea and Vacchiano, Veria and Liguori, Rocco and Blennow, Kaj and Zetterberg, Henrik and Mattsson-Carlgren, Niklas and Gonzalez-Ortiz, Fernando and Parchi, Piero and Andersen, Peter Munch and Hansson, Oskar}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; amyotrophic lateral sclerosis; biomarker; blood; low-molecular-weight tau; p-tau}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{A comparison of p-tau assays for the specificity to detect tau changes in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.70208}},
  doi          = {{10.1002/alz.70208}},
  volume       = {{21}},
  year         = {{2025}},
}