Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment
IntroductionPlasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer’s disease (AD) assessment is unclear.MethodsAβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecu...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1364658/full |
| _version_ | 1797246742071083008 |
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| author | Darren M. Weber Steven W. Taylor Robert J. Lagier Jueun C. Kim Scott M. Goldman Nigel J. Clarke David E. Vaillancourt Ranjan Duara Ranjan Duara Karen N. McFarland Wei-en Wang Todd E. Golde Todd E. Golde Michael K. Racke |
| author_facet | Darren M. Weber Steven W. Taylor Robert J. Lagier Jueun C. Kim Scott M. Goldman Nigel J. Clarke David E. Vaillancourt Ranjan Duara Ranjan Duara Karen N. McFarland Wei-en Wang Todd E. Golde Todd E. Golde Michael K. Racke |
| author_sort | Darren M. Weber |
| collection | DOAJ |
| description | IntroductionPlasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer’s disease (AD) assessment is unclear.MethodsAβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.ResultsHigh diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs. negative Aβ-PET results. Assuming a moderate prevalence of Aβ-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients’ cognitive impairment and help reduce PET evaluation by about 40%.ConclusionHigh-throughput plasma Aβ42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings. |
| first_indexed | 2024-04-24T19:47:38Z |
| format | Article |
| id | doaj.art-9e471991a0474d5183e46f090a18bcfb |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-24T19:47:38Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-9e471991a0474d5183e46f090a18bcfb2024-03-25T04:24:22ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-03-011510.3389/fneur.2024.13646581364658Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessmentDarren M. Weber0Steven W. Taylor1Robert J. Lagier2Jueun C. Kim3Scott M. Goldman4Nigel J. Clarke5David E. Vaillancourt6Ranjan Duara7Ranjan Duara8Karen N. McFarland9Wei-en Wang10Todd E. Golde11Todd E. Golde12Michael K. Racke13Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesDepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United StatesDepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United StatesWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, United StatesDepartment of Neurology, Center for Translational Research in Neurodegenerative Disease, 1Florida Alzheimer’s Disease Research Center (ADRC), University of Florida, Gainesville, FL, United StatesDepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United StatesDepartment of Neurology, Center for Translational Research in Neurodegenerative Disease, 1Florida Alzheimer’s Disease Research Center (ADRC), University of Florida, Gainesville, FL, United StatesDepartment of Pharmacology and Chemical Biology, Department of Neurology, Emory Center for Neurodegenerative Disease, Emory University, Atlanta, GA, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United StatesIntroductionPlasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer’s disease (AD) assessment is unclear.MethodsAβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.ResultsHigh diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs. negative Aβ-PET results. Assuming a moderate prevalence of Aβ-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients’ cognitive impairment and help reduce PET evaluation by about 40%.ConclusionHigh-throughput plasma Aβ42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.https://www.frontiersin.org/articles/10.3389/fneur.2024.1364658/fullAlzheimer’s diseasebeta-amyloidblood biomarkersLC-MS/MSPETprescreening |
| spellingShingle | Darren M. Weber Steven W. Taylor Robert J. Lagier Jueun C. Kim Scott M. Goldman Nigel J. Clarke David E. Vaillancourt Ranjan Duara Ranjan Duara Karen N. McFarland Wei-en Wang Todd E. Golde Todd E. Golde Michael K. Racke Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment Frontiers in Neurology Alzheimer’s disease beta-amyloid blood biomarkers LC-MS/MS PET prescreening |
| title | Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment |
| title_full | Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment |
| title_fullStr | Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment |
| title_full_unstemmed | Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment |
| title_short | Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment |
| title_sort | clinical utility of plasma aβ42 40 ratio by lc ms ms in alzheimer s disease assessment |
| topic | Alzheimer’s disease beta-amyloid blood biomarkers LC-MS/MS PET prescreening |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1364658/full |
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