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Highly Accurate Blood Test for Alzheimer's Disease Comparable or Superior to Clinical CSF Tests

Barthélemy, Nicolas R ; Salvadó, Gemma LU ; Schindler, Suzanne ; He, Yingxin ; Janelidze, Shorena LU ; Collij, Lyduine E LU ; Saef, Benjamin ; Henson, Rachel L ; Chen, Charles D and Gordon, Brian A , et al. (2024) In Nature Medicine
Abstract

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using PET... (More)

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using PET imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area-under-the-curve (AUC) for both between 0.95-0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired sub-cohorts (BioFINDER-2: n=720; Knight ADRC: n=50), plasma %p-tau217 had an accuracy, positive predictive value and negative predictive value of 89-90% for Aβ PET and 87-88% for tau-PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two cut-off approach. Blood plasma %p-tau217 demonstrated performance clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Alzheimer's disease, Diagnosis, Diagnostic markers
in
Nature Medicine
pages
42 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85186947224
  • pmid:38382645
ISSN
1546-170X
DOI
10.1038/s41591-024-02869-z
language
English
LU publication?
yes
id
260d917a-8484-4125-8903-2a76b0e06ad2
date added to LUP
2024-02-26 17:19:22
date last changed
2024-04-21 06:33:05
@article{260d917a-8484-4125-8903-2a76b0e06ad2,
  abstract     = {{<p>With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using PET imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area-under-the-curve (AUC) for both between 0.95-0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired sub-cohorts (BioFINDER-2: n=720; Knight ADRC: n=50), plasma %p-tau217 had an accuracy, positive predictive value and negative predictive value of 89-90% for Aβ PET and 87-88% for tau-PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two cut-off approach. Blood plasma %p-tau217 demonstrated performance clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.</p>}},
  author       = {{Barthélemy, Nicolas R and Salvadó, Gemma and Schindler, Suzanne and He, Yingxin and Janelidze, Shorena and Collij, Lyduine E and Saef, Benjamin and Henson, Rachel L and Chen, Charles D and Gordon, Brian A and Li, Yan and La Joie, Renaud and Benzinger, Tammie L S and Morris, John C and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Ossenkoppele, Rik and Rabinovici, Gil D and Stomrud, Erik and Bateman, Randall J and Hansson, Oskar}},
  issn         = {{1546-170X}},
  keywords     = {{Alzheimer's disease; Diagnosis; Diagnostic markers}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Highly Accurate Blood Test for Alzheimer's Disease Comparable or Superior to Clinical CSF Tests}},
  url          = {{http://dx.doi.org/10.1038/s41591-024-02869-z}},
  doi          = {{10.1038/s41591-024-02869-z}},
  year         = {{2024}},
}