Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease

Min Shi; Lu Tang; Jon B. Toledo; Carmen Ginghina; Hua Wang; Patrick Aro; Poul H. Jensen; Daniel Weintraub; Alice S. Chen-Plotkin; David J. Irwin; Murray Grossman; Leo McCluskey; Lauren B. Elman; David A. Wolk; Edward B. Lee; Leslie M. Shaw; John Q. Trojanowski; Jing Zhang

doi:10.1016/j.jalz.2018.02.015

Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease

Min Shi, Lu Tang, Jon B. Toledo, Carmen Ginghina, Hua Wang, Patrick Aro, Poul H. Jensen, Daniel Weintraub, Alice S. Chen-Plotkin, David J. Irwin, Murray Grossman, Leo McCluskey, Lauren B. Elman, David A. Wolk, Edward B. Lee, Leslie M. Shaw, John Q. Trojanowski, Jing Zhang

Houston Methodist

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

39 Scopus citations

Abstract

Introduction: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1–42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. Methods: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. Results: CSF total α-syn, when combined with amyloid β peptide 1–42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. Discussion: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.

Original language	English (US)
Pages (from-to)	1052-1062
Number of pages	11
Journal	Alzheimer's and Dementia
Volume	14
Issue number	8
DOIs	https://doi.org/10.1016/j.jalz.2018.02.015
State	Published - Aug 2018

Keywords

Alzheimer's disease
Biomarkers
Cerebrospinal fluid
Differential diagnosis
α-synuclein

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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10.1016/j.jalz.2018.02.015

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Shi, M., Tang, L., Toledo, J. B., Ginghina, C., Wang, H., Aro, P., Jensen, P. H., Weintraub, D., Chen-Plotkin, A. S., Irwin, D. J., Grossman, M., McCluskey, L., Elman, L. B., Wolk, D. A., Lee, E. B., Shaw, L. M., Trojanowski, J. Q., & Zhang, J. (2018). Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease. Alzheimer's and Dementia, 14(8), 1052-1062. https://doi.org/10.1016/j.jalz.2018.02.015

Shi, M, Tang, L, Toledo, JB, Ginghina, C, Wang, H, Aro, P, Jensen, PH, Weintraub, D, Chen-Plotkin, AS, Irwin, DJ, Grossman, M, McCluskey, L, Elman, LB, Wolk, DA, Lee, EB, Shaw, LM, Trojanowski, JQ & Zhang, J 2018, 'Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease', Alzheimer's and Dementia, vol. 14, no. 8, pp. 1052-1062. https://doi.org/10.1016/j.jalz.2018.02.015

@article{921d029fb1ff488f81585575f1a91aaa,

title = "Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease",

abstract = "Introduction: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1–42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. Methods: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. Results: CSF total α-syn, when combined with amyloid β peptide 1–42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. Discussion: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.",

keywords = "Alzheimer's disease, Biomarkers, Cerebrospinal fluid, Differential diagnosis, α-synuclein",

author = "Min Shi and Lu Tang and Toledo, {Jon B.} and Carmen Ginghina and Hua Wang and Patrick Aro and Jensen, {Poul H.} and Daniel Weintraub and Chen-Plotkin, {Alice S.} and Irwin, {David J.} and Murray Grossman and Leo McCluskey and Elman, {Lauren B.} and Wolk, {David A.} and Lee, {Edward B.} and Shaw, {Leslie M.} and Trojanowski, {John Q.} and Jing Zhang",

note = "Funding Information: The authors deeply appreciate the participants for their generous donation of samples. This study was supported by grants from the National Institutes of Health (NIH) (U01 NS082137, U01 NS091272, and R56 AG057417 to J.Z., and P30 AG010124, P50 NS053488, and P01 AG017586-8499 to J.Q.T.) and grants from China (Z161100000216150, 2016YFC1306502 and XDA12040101 to J.Z.) The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2018 the Alzheimer's Association",

year = "2018",

month = aug,

doi = "10.1016/j.jalz.2018.02.015",

language = "English (US)",

volume = "14",

pages = "1052--1062",

journal = "Alzheimer's and Dementia",

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TY - JOUR

T1 - Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease

AU - Shi, Min

AU - Tang, Lu

AU - Toledo, Jon B.

AU - Ginghina, Carmen

AU - Wang, Hua

AU - Aro, Patrick

AU - Jensen, Poul H.

AU - Weintraub, Daniel

AU - Chen-Plotkin, Alice S.

AU - Irwin, David J.

AU - Grossman, Murray

AU - McCluskey, Leo

AU - Elman, Lauren B.

AU - Wolk, David A.

AU - Lee, Edward B.

AU - Shaw, Leslie M.

AU - Trojanowski, John Q.

AU - Zhang, Jing

N1 - Funding Information: The authors deeply appreciate the participants for their generous donation of samples. This study was supported by grants from the National Institutes of Health (NIH) (U01 NS082137, U01 NS091272, and R56 AG057417 to J.Z., and P30 AG010124, P50 NS053488, and P01 AG017586-8499 to J.Q.T.) and grants from China (Z161100000216150, 2016YFC1306502 and XDA12040101 to J.Z.) The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: © 2018 the Alzheimer's Association

PY - 2018/8

Y1 - 2018/8

N2 - Introduction: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1–42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. Methods: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. Results: CSF total α-syn, when combined with amyloid β peptide 1–42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. Discussion: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.

AB - Introduction: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1–42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. Methods: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. Results: CSF total α-syn, when combined with amyloid β peptide 1–42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. Discussion: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.

KW - Alzheimer's disease

KW - Biomarkers

KW - Cerebrospinal fluid

KW - Differential diagnosis

KW - α-synuclein

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SN - 1552-5260

VL - 14

SP - 1052

EP - 1062

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 8

ER -

Cerebrospinal fluid α-synuclein contributes to the differential diagnosis of Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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