Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity

Jung Min Pyun; Young Ho Park; Young Chul Youn; Min Ju Kang; Kyu Hwan Shim; Jae Won Jang; Jihwan You; Kwangsik Nho; Sang Yun Kim; Michael W. Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; William Jagust; John Q. Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Andrew J. Saykin; John Morris; Leslie M. Shaw; Greg Sorensen; Maria Carrillo; Lew Kuller; Marc Raichle; Steven Paul; Peter Davies; Howard Fillit; Franz Hefti; David Holtzman; M. Marcel Mesulam; William Potter; Peter Snyder; James Hendrix; Aparna Vasanthakumar; Tom Montine; Michael Rafii; Tiffany Chow; Rema Raman; Gustavo Jimenez; Michael Donohue; Devon Gessert; Kelly Harless; Jennifer Salazar; Yuliana Cabrera; Sarah Walter; Lindsey Hergesheimer; Danielle Harvey; Michael Donohue; Matthew Bernstein; Nick Fox; Paul Thompson; Norbert Schuff; Charles DeCArli; Bret Borowski; Jeff Gunter; Matt Senjem; Prashanthi Vemuri; David Jones; Kejal Kantarci; Chad Ward; Robert A. Koeppe; Norm Foster; Eric M. Reiman; Kewei Chen; Chet Mathis; Susan Landau; Nigel J. Cairns; Erin Franklin; Virginia Lee; Magdalena Korecka; Michal Figurski; Karen Crawford; Scott Neu; Tatiana M. Foroud; Steven Potkin; Li Shen; Kelley Faber; Sungeun Kim; Marilyn Albert; Richard Frank; John Hsiao; Zaven Khachaturian

doi:10.1038/s41398-024-02766-6

Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity

Jung Min Pyun, Young Ho Park, Young Chul Youn, Min Ju Kang, Kyu Hwan Shim, Jae Won Jang, Jihwan You, Kwangsik Nho, Sang Yun Kim, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John MorrisLeslie M. Shaw, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, James Hendrix, Aparna Vasanthakumar, Tom Montine, Michael Rafii, Tiffany Chow, Rema Raman, Gustavo Jimenez, Michael Donohue, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Danielle Harvey, Michael Donohue, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Franklin, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Marilyn Albert, Richard Frank, John Hsiao, Zaven Khachaturian

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

Abstract

Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET−/plasma−, PET−/plasma+, PET+/plasma−, PET+/plasma+) using Alzheimer’s Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET−/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET−/plasma+ showed intermediate changes between PET−/plasma− and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma− represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET−/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.

Original language	English (US)
Article number	88
Journal	Translational psychiatry
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41398-024-02766-6
State	Published - Dec 2024

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

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Pyun, J. M., Park, Y. H., Youn, Y. C., Kang, M. J., Shim, K. H., Jang, J. W., You, J., Nho, K., Kim, S. Y., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., ... Khachaturian, Z. (2024). Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity. Translational psychiatry, 14(1), Article 88. https://doi.org/10.1038/s41398-024-02766-6

Pyun, JM, Park, YH, Youn, YC, Kang, MJ, Shim, KH, Jang, JW, You, J, Nho, K, Kim, SY, Weiner, MW, Aisen, P, Petersen, R , Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Shaw, LM, Sorensen, G, Carrillo, M, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulam, MM, Potter, W, Snyder, P, Hendrix, J, Vasanthakumar, A, Montine, T, Rafii, M, Chow, T, Raman, R, Jimenez, G, Donohue, M, Gessert, D, Harless, K, Salazar, J, Cabrera, Y, Walter, S, Hergesheimer, L, Harvey, D, Donohue, M, Bernstein, M, Fox, N, Thompson, P, Schuff, N, DeCArli, C, Borowski, B, Gunter, J, Senjem, M, Vemuri, P , Jones, D , Kantarci, K, Ward, C, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Franklin, E, Lee, V, Korecka, M, Figurski, M, Crawford, K, Neu, S, Foroud, TM, Potkin, S, Shen, L, Faber, K, Kim, S, Albert, M, Frank, R, Hsiao, J & Khachaturian, Z 2024, 'Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity', Translational psychiatry, vol. 14, no. 1, 88. https://doi.org/10.1038/s41398-024-02766-6

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title = "Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity",

abstract = "Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET−/plasma−, PET−/plasma+, PET+/plasma−, PET+/plasma+) using Alzheimer{\textquoteright}s Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET−/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET−/plasma+ showed intermediate changes between PET−/plasma− and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma− represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET−/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.",

author = "Pyun, {Jung Min} and Park, {Young Ho} and Youn, {Young Chul} and Kang, {Min Ju} and Shim, {Kyu Hwan} and Jang, {Jae Won} and Jihwan You and Kwangsik Nho and Kim, {Sang Yun} and Weiner, {Michael W.} and Paul Aisen and Ronald Petersen and Jack, {Clifford R.} and William Jagust and Trojanowki, {John Q.} and Toga, {Arthur W.} and Laurel Beckett and Green, {Robert C.} and Saykin, {Andrew J.} and John Morris and Shaw, {Leslie M.} and Greg Sorensen and Maria Carrillo and Lew Kuller and Marc Raichle and Steven Paul and Peter Davies and Howard Fillit and Franz Hefti and David Holtzman and Mesulam, {M. Marcel} and William Potter and Peter Snyder and James Hendrix and Aparna Vasanthakumar and Tom Montine and Michael Rafii and Tiffany Chow and Rema Raman and Gustavo Jimenez and Michael Donohue and Devon Gessert and Kelly Harless and Jennifer Salazar and Yuliana Cabrera and Sarah Walter and Lindsey Hergesheimer and Danielle Harvey and Michael Donohue and Matthew Bernstein and Nick Fox and Paul Thompson and Norbert Schuff and Charles DeCArli and Bret Borowski and Jeff Gunter and Matt Senjem and Prashanthi Vemuri and David Jones and Kejal Kantarci and Chad Ward and Koeppe, {Robert A.} and Norm Foster and Reiman, {Eric M.} and Kewei Chen and Chet Mathis and Susan Landau and Cairns, {Nigel J.} and Erin Franklin and Virginia Lee and Magdalena Korecka and Michal Figurski and Karen Crawford and Scott Neu and Foroud, {Tatiana M.} and Steven Potkin and Li Shen and Kelley Faber and Sungeun Kim and Marilyn Albert and Richard Frank and John Hsiao and Zaven Khachaturian",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41398-024-02766-6",

language = "English (US)",

volume = "14",

journal = "Translational psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity

AU - Pyun, Jung Min

AU - Park, Young Ho

AU - Youn, Young Chul

AU - Kang, Min Ju

AU - Shim, Kyu Hwan

AU - Jang, Jae Won

AU - You, Jihwan

AU - Nho, Kwangsik

AU - Kim, Sang Yun

AU - Weiner, Michael W.

AU - Aisen, Paul

AU - Petersen, Ronald

AU - Jack, Clifford R.

AU - Jagust, William

AU - Trojanowki, John Q.

AU - Toga, Arthur W.

AU - Beckett, Laurel

AU - Green, Robert C.

AU - Saykin, Andrew J.

AU - Morris, John

AU - Shaw, Leslie M.

AU - Sorensen, Greg

AU - Carrillo, Maria

AU - Kuller, Lew

AU - Raichle, Marc

AU - Paul, Steven

AU - Davies, Peter

AU - Fillit, Howard

AU - Hefti, Franz

AU - Holtzman, David

AU - Mesulam, M. Marcel

AU - Potter, William

AU - Snyder, Peter

AU - Hendrix, James

AU - Vasanthakumar, Aparna

AU - Montine, Tom

AU - Rafii, Michael

AU - Chow, Tiffany

AU - Raman, Rema

AU - Jimenez, Gustavo

AU - Donohue, Michael

AU - Gessert, Devon

AU - Harless, Kelly

AU - Salazar, Jennifer

AU - Cabrera, Yuliana

AU - Walter, Sarah

AU - Hergesheimer, Lindsey

AU - Harvey, Danielle

AU - Donohue, Michael

AU - Bernstein, Matthew

AU - Fox, Nick

AU - Thompson, Paul

AU - Schuff, Norbert

AU - DeCArli, Charles

AU - Borowski, Bret

AU - Gunter, Jeff

AU - Senjem, Matt

AU - Vemuri, Prashanthi

AU - Jones, David

AU - Kantarci, Kejal

AU - Ward, Chad

AU - Koeppe, Robert A.

AU - Foster, Norm

AU - Reiman, Eric M.

AU - Chen, Kewei

AU - Mathis, Chet

AU - Landau, Susan

AU - Cairns, Nigel J.

AU - Franklin, Erin

AU - Lee, Virginia

AU - Korecka, Magdalena

AU - Figurski, Michal

AU - Crawford, Karen

AU - Neu, Scott

AU - Foroud, Tatiana M.

AU - Potkin, Steven

AU - Shen, Li

AU - Faber, Kelley

AU - Kim, Sungeun

AU - Albert, Marilyn

AU - Frank, Richard

AU - Hsiao, John

AU - Khachaturian, Zaven

PY - 2024/12

Y1 - 2024/12

N2 - Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET−/plasma−, PET−/plasma+, PET+/plasma−, PET+/plasma+) using Alzheimer’s Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET−/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET−/plasma+ showed intermediate changes between PET−/plasma− and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma− represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET−/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.

AB - Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET−/plasma−, PET−/plasma+, PET+/plasma−, PET+/plasma+) using Alzheimer’s Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET−/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET−/plasma+ showed intermediate changes between PET−/plasma− and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma− represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET−/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.

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Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivity

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