Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls

Ryan T. Muir; Sophie Stukas; Jennifer G. Cooper; Andrew E. Beaudin; Cheryl R. McCreary; Myrlene Gee; Krista Nelles; Nikita Nukala; Janina Valencia; Kristopher M. Kirmess; Sandra E. Black; Michael D. Hill; Richard Camicioli; Cheryl L. Wellington; Eric E. Smith

doi:10.1002/alz.70010

Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls

Ryan T. Muir
, Sophie Stukas
, Jennifer G. Cooper
, Andrew E. Beaudin
, Cheryl R. McCreary
, Myrlene Gee
, Krista Nelles
, Nikita Nukala
, Janina Valencia
, Kristopher M. Kirmess
, Sandra E. Black
, Michael D. Hill
, Richard Camicioli
, Cheryl L. Wellington
, Eric E. Smith^*

^*Corresponding author for this work

University of Calgary
University of Calgary
University of Calgary
University of Toronto
University of British Columbia
University of Alberta
C2N Diagnostics

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

7 Scopus citations

Abstract

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ_42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls. METHODS: Plasma Aβ_42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ_42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS: Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ_42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ_42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95% confidence interval: 0.80, 0.95). DISCUSSION: Plasma Aβ_42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls. Highlights: Participants with CAA had reduced plasma Aβ_42/40 ratios compared to controls. Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls. Plasma GFAP was similar in CAA and controls. Together, plasma Aβ_42/40, p-tau-181, and NfL had excellent discriminability for CAA.

Original language	English
Article number	e70010
Journal	Alzheimer's and Dementia
Volume	21
Issue number	3
DOIs	https://doi.org/10.1002/alz.70010
State	Published - Mar 2025
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer's disease
beta-amyloid
cerebral amyloid angiopathy
glial fibrillary acidic protein
hemorrhagic stroke
neurofilament light chain
phosphorylated tau
plasma biomarkers

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10.1002/alz.70010

Cite this

Muir, R. T., Stukas, S., Cooper, J. G., Beaudin, A. E., McCreary, C. R., Gee, M., Nelles, K., Nukala, N., Valencia, J., Kirmess, K. M., Black, S. E., Hill, M. D., Camicioli, R., Wellington, C. L., & Smith, E. E. (2025). Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls. Alzheimer's and Dementia, 21(3), Article e70010. https://doi.org/10.1002/alz.70010

@article{083ee82875524c85ba12b3c7f6874e13,

title = "Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls",

abstract = "INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls. METHODS: Plasma Aβ42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS: Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95\% confidence interval: 0.80, 0.95). DISCUSSION: Plasma Aβ42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls. Highlights: Participants with CAA had reduced plasma Aβ42/40 ratios compared to controls. Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls. Plasma GFAP was similar in CAA and controls. Together, plasma Aβ42/40, p-tau-181, and NfL had excellent discriminability for CAA.",

keywords = "Alzheimer's disease, beta-amyloid, cerebral amyloid angiopathy, glial fibrillary acidic protein, hemorrhagic stroke, neurofilament light chain, phosphorylated tau, plasma biomarkers",

author = "Muir, \{Ryan T.\} and Sophie Stukas and Cooper, \{Jennifer G.\} and Beaudin, \{Andrew E.\} and McCreary, \{Cheryl R.\} and Myrlene Gee and Krista Nelles and Nikita Nukala and Janina Valencia and Kirmess, \{Kristopher M.\} and Black, \{Sandra E.\} and Hill, \{Michael D.\} and Richard Camicioli and Wellington, \{Cheryl L.\} and Smith, \{Eric E.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = mar,

doi = "10.1002/alz.70010",

language = "Ingl{\'e}s",

volume = "21",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc",

number = "3",

}

Muir, RT, Stukas, S, Cooper, JG, Beaudin, AE, McCreary, CR, Gee, M, Nelles, K, Nukala, N, Valencia, J, Kirmess, KM, Black, SE, Hill, MD, Camicioli, R, Wellington, CL & Smith, EE 2025, 'Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls', Alzheimer's and Dementia, vol. 21, no. 3, e70010. https://doi.org/10.1002/alz.70010

TY - JOUR

T1 - Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls

AU - Muir, Ryan T.

AU - Stukas, Sophie

AU - Cooper, Jennifer G.

AU - Beaudin, Andrew E.

AU - McCreary, Cheryl R.

AU - Gee, Myrlene

AU - Nelles, Krista

AU - Nukala, Nikita

AU - Valencia, Janina

AU - Kirmess, Kristopher M.

AU - Black, Sandra E.

AU - Hill, Michael D.

AU - Camicioli, Richard

AU - Wellington, Cheryl L.

AU - Smith, Eric E.

PY - 2025/3

Y1 - 2025/3

N2 - INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls. METHODS: Plasma Aβ42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS: Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95% confidence interval: 0.80, 0.95). DISCUSSION: Plasma Aβ42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls. Highlights: Participants with CAA had reduced plasma Aβ42/40 ratios compared to controls. Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls. Plasma GFAP was similar in CAA and controls. Together, plasma Aβ42/40, p-tau-181, and NfL had excellent discriminability for CAA.

AB - INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls. METHODS: Plasma Aβ42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS: Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95% confidence interval: 0.80, 0.95). DISCUSSION: Plasma Aβ42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls. Highlights: Participants with CAA had reduced plasma Aβ42/40 ratios compared to controls. Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls. Plasma GFAP was similar in CAA and controls. Together, plasma Aβ42/40, p-tau-181, and NfL had excellent discriminability for CAA.

KW - Alzheimer's disease

KW - beta-amyloid

KW - cerebral amyloid angiopathy

KW - glial fibrillary acidic protein

KW - hemorrhagic stroke

KW - neurofilament light chain

KW - phosphorylated tau

KW - plasma biomarkers

UR - https://www.scopus.com/pages/publications/105002039751

U2 - 10.1002/alz.70010

DO - 10.1002/alz.70010

M3 - Artículo

C2 - 40156276

AN - SCOPUS:105002039751

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 3

M1 - e70010

ER -

Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls

Abstract

UN SDGs

Keywords

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