Validation of Plasma Amyloid-β 42/40 for Detecting Alzheimer Disease Amyloid Plaques.

Alzheimer Disease / diagnostic imaging Amyloid beta-Peptides Biomarkers Humans Peptide Fragments Plaque, Amyloid Positron-Emission Tomography

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
15 02 2022
Historique:
received: 22 06 2021
accepted: 06 12 2021
pubmed: 16 12 2021
medline: 6 4 2022
entrez: 15 12 2021
Statut: ppublish

Résumé

To determine the diagnostic accuracy of a plasma Aβ42/Aβ40 assay in classifying amyloid PET status across global research studies using samples collected by multiple centers that utilize different blood collection and processing protocols. Plasma samples (n = 465) were obtained from 3 large Alzheimer disease (AD) research cohorts in the United States (n = 182), Australia (n = 183), and Sweden (n = 100). Plasma Aβ42/Aβ40 was measured by a high precision immunoprecipitation mass spectrometry (IPMS) assay and compared to the reference standards of amyloid PET and CSF Aβ42/Aβ40. In the combined cohort of 465 participants, plasma Aβ42/Aβ40 had good concordance with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.80-0.87); concordance improved with the inclusion of Plasma Aβ42/Aβ40 is a robust measure for detecting amyloid plaques and can be utilized to aid in the diagnosis of AD, identify those at risk for future dementia due to AD, and improve the diversity of populations enrolled in AD research and clinical trials. This study provides Class II evidence that plasma Aβ42/Aβ40, as measured by a high precision IPMS assay, accurately diagnoses brain amyloidosis in both cognitively unimpaired and impaired research participants.

Sections du résumé

BACKGROUND AND OBJECTIVES
To determine the diagnostic accuracy of a plasma Aβ42/Aβ40 assay in classifying amyloid PET status across global research studies using samples collected by multiple centers that utilize different blood collection and processing protocols.
METHODS
Plasma samples (n = 465) were obtained from 3 large Alzheimer disease (AD) research cohorts in the United States (n = 182), Australia (n = 183), and Sweden (n = 100). Plasma Aβ42/Aβ40 was measured by a high precision immunoprecipitation mass spectrometry (IPMS) assay and compared to the reference standards of amyloid PET and CSF Aβ42/Aβ40.
RESULTS
In the combined cohort of 465 participants, plasma Aβ42/Aβ40 had good concordance with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.80-0.87); concordance improved with the inclusion of
DISCUSSION
Plasma Aβ42/Aβ40 is a robust measure for detecting amyloid plaques and can be utilized to aid in the diagnosis of AD, identify those at risk for future dementia due to AD, and improve the diversity of populations enrolled in AD research and clinical trials.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that plasma Aβ42/Aβ40, as measured by a high precision IPMS assay, accurately diagnoses brain amyloidosis in both cognitively unimpaired and impaired research participants.

Identifiants

DOI: 10.1212/WNL.0000000000013211 PMID: 34906975 PMC: PMC8865895
pubmed: 34906975
pii: WNL.0000000000013211
doi: 10.1212/WNL.0000000000013211
pmc: PMC8865895
doi:

Substances chimiques

Amyloid beta-Peptides 0
Biomarkers 0
Peptide Fragments 0
amyloid beta-protein (1-42) 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e688-e699

Subventions

Organisme : NIA NIH HHS
ID : R56 AG061900
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG053426
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061900
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072979
Pays : United States

Informations de copyright

© 2021 American Academy of Neurology.

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Auteurs

Yan Li (Y)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Suzanne E Schindler (SE)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

James G Bollinger (JG)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Vitaliy Ovod (V)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Kwasi G Mawuenyega (KG)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Michael W Weiner (MW)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Leslie M Shaw (LM)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Colin L Masters (CL)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Christopher J Fowler (CJ)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

John Q Trojanowski (JQ)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Magdalena Korecka (M)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Ralph N Martins (RN)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Shorena Janelidze (S)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Oskar Hansson (O)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden.

Randall J Bateman (RJ)

From the Department of Neurology (Y.L., S.E.S., J.G.B., V.O., K.G.M., R.J.B.), Division of Biostatistics (Y.L.), Knight Alzheimer's Disease Research Center (S.E.S., R.J.B.), and Hope Center for Neurological Disorders (R.J.B.), Washington University School of Medicine, St. Louis, MO; Departments of Psychiatry, Radiology and Biomedical Imaging, Medicine, and Neurology (M.W.W.), Center for Imaging and Neurodegenerative Diseases, Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, University of California San Francisco; Department of Pathology and Laboratory Medicine (S.M.L., J.Q.T., M.K.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; The Florey Institute of Neuroscience and Mental Health (C.L.M., C.J.F.), University of Melbourne, Victoria; Edith Cowan University (R.N.M.), Joondalup, Australia; Department of Clinical Sciences, Clinical Memory Research Unit (S.J., O.H.), Lund University; and Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden. batemanr@wustl.edu.
ORCID: 0000-0002-7729-1702

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Validation of Plasma Amyloid-β 42/40 for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Validation of Plasma Amyloid-β 42/40 for...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Validation of Plasma Amyloid-β 42/40 for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Validation of Plasma Amyloid-β 42/40 for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Fragments peptidiques › Validation of Plasma Amyloid-β 42/40 for...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Plaque amyloïde › Validation of Plasma Amyloid-β 42/40 for...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Validation of Plasma Amyloid-β 42/40 for...