Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid

Matthew R. Meyer; Kristopher M. Kirmess; Stephanie Eastwood; Traci L. Wente-Roth; Faith Irvin; Mary S. Holubasch; Venky Venkatesh; Ilana Fogelman; Mark Monane; Lucy Hanna; Gil D. Rabinovici; Barry A. Siegel; Rachel A. Whitmer; Charles Apgar; Randall J. Bateman; David M. Holtzman; Michael Irizarry; David Verbel; Pallavi Sachdev; Satoshi Ito; John Contois; Kevin E. Yarasheski; Joel B. Braunstein; Philip B. Verghese; Tim West

doi:10.1002/alz.13764

Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid

Matthew R. Meyer, Kristopher M. Kirmess, Stephanie Eastwood, Traci L. Wente-Roth, Faith Irvin, Mary S. Holubasch, Venky Venkatesh, Ilana Fogelman, Mark Monane, Lucy Hanna, Gil D. Rabinovici, Barry A. Siegel, Rachel A. Whitmer, Charles Apgar, Randall J. Bateman, David M. Holtzman, Michael Irizarry, David Verbel, Pallavi Sachdev, Satoshi ItoJohn Contois, Kevin E. Yarasheski, Joel B. Braunstein, Philip B. Verghese, Tim West

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

Original language	English
Pages (from-to)	3179-3192
Number of pages	14
Journal	Alzheimer's and Dementia
Volume	20
Issue number	5
DOIs	https://doi.org/10.1002/alz.13764
State	Published - May 2024

Keywords

Alzheimer's
amyloid beta
blood biomarker
clinical validity
diagnostic
p-tau217

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10.1002/alz.13764

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Meyer, M. R., Kirmess, K. M., Eastwood, S., Wente-Roth, T. L., Irvin, F., Holubasch, M. S., Venkatesh, V., Fogelman, I., Monane, M., Hanna, L., Rabinovici, G. D., Siegel, B. A., Whitmer, R. A., Apgar, C., Bateman, R. J., Holtzman, D. M., Irizarry, M., Verbel, D., Sachdev, P., ... West, T. (2024). Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid. Alzheimer's and Dementia, 20(5), 3179-3192. https://doi.org/10.1002/alz.13764

@article{3927e05d0c4442ccbc73aadc0367dd4a,

title = "Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid",

abstract = "BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.",

keywords = "Alzheimer's, amyloid beta, blood biomarker, clinical validity, diagnostic, p-tau217",

author = "Meyer, {Matthew R.} and Kirmess, {Kristopher M.} and Stephanie Eastwood and Wente-Roth, {Traci L.} and Faith Irvin and Holubasch, {Mary S.} and Venky Venkatesh and Ilana Fogelman and Mark Monane and Lucy Hanna and Rabinovici, {Gil D.} and Siegel, {Barry A.} and Whitmer, {Rachel A.} and Charles Apgar and Bateman, {Randall J.} and Holtzman, {David M.} and Michael Irizarry and David Verbel and Pallavi Sachdev and Satoshi Ito and John Contois and Yarasheski, {Kevin E.} and Braunstein, {Joel B.} and Verghese, {Philip B.} and Tim West",

note = "Publisher Copyright: {\textcopyright} 2024 C2N Diagnostics LLC. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = may,

doi = "10.1002/alz.13764",

language = "English",

volume = "20",

pages = "3179--3192",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

number = "5",

}

Meyer, MR, Kirmess, KM, Eastwood, S, Wente-Roth, TL, Irvin, F, Holubasch, MS, Venkatesh, V, Fogelman, I, Monane, M, Hanna, L, Rabinovici, GD, Siegel, BA, Whitmer, RA, Apgar, C, Bateman, RJ , Holtzman, DM, Irizarry, M, Verbel, D, Sachdev, P, Ito, S, Contois, J, Yarasheski, KE, Braunstein, JB, Verghese, PB & West, T 2024, 'Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid', Alzheimer's and Dementia, vol. 20, no. 5, pp. 3179-3192. https://doi.org/10.1002/alz.13764

Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid. / Meyer, Matthew R.; Kirmess, Kristopher M.; Eastwood, Stephanie et al.
In: Alzheimer's and Dementia, Vol. 20, No. 5, 05.2024, p. 3179-3192.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Clinical validation of the PrecivityAD2 blood test

T2 - A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid

AU - Meyer, Matthew R.

AU - Kirmess, Kristopher M.

AU - Eastwood, Stephanie

AU - Wente-Roth, Traci L.

AU - Irvin, Faith

AU - Holubasch, Mary S.

AU - Venkatesh, Venky

AU - Fogelman, Ilana

AU - Monane, Mark

AU - Hanna, Lucy

AU - Rabinovici, Gil D.

AU - Siegel, Barry A.

AU - Whitmer, Rachel A.

AU - Apgar, Charles

AU - Bateman, Randall J.

AU - Holtzman, David M.

AU - Irizarry, Michael

AU - Verbel, David

AU - Sachdev, Pallavi

AU - Ito, Satoshi

AU - Contois, John

AU - Yarasheski, Kevin E.

AU - Braunstein, Joel B.

AU - Verghese, Philip B.

AU - West, Tim

PY - 2024/5

Y1 - 2024/5

N2 - BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

AB - BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

KW - Alzheimer's

KW - amyloid beta

KW - blood biomarker

KW - clinical validity

KW - diagnostic

KW - p-tau217

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U2 - 10.1002/alz.13764

DO - 10.1002/alz.13764

M3 - Article

C2 - 38491912

AN - SCOPUS:85188435711

SN - 1552-5260

VL - 20

SP - 3179

EP - 3192

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 5

ER -

Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid

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