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. 2025 Mar;21(3):e70010.
doi: 10.1002/alz.70010.

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

Ryan T Muir  1   2   3   4   5 , Sophie Stukas  6 , Jennifer G Cooper  6 , Andrew E Beaudin  2   4 , Cheryl R McCreary  2   4   7 , Myrlene Gee  8 , Krista Nelles  8 , Nikita Nukala  4 , Janina Valencia  4 , Kristopher M Kirmess  9 , Sandra E Black  5 , Michael D Hill  1   2   3 , Richard Camicioli  8   10 , Cheryl L Wellington  6 , Eric E Smith  1   2   3   4
Affiliations

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

Ryan T Muir et al. Alzheimers Dement. 2025 Mar.

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.

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Conflict of interest statement

R.T.M.: does not have any perceived or actual conflicts of interest relevant to this work. S.S.: does not have any perceived or actual conflicts of interest relevant to this work. J.G.C.: does not have any perceived or actual conflicts of interest relevant to this work. A.E.B.: does not have any perceived or actual conflicts of interest relevant to this work. C.R.M.: does not have any perceived or actual conflicts of interest relevant to this work. M.G.: does not have any perceived or actual conflicts of interest relevant to this work. K.N.: does not have any perceived or actual conflicts of interest relevant to this work. N.N.: does not have any perceived or actual conflicts of interest relevant to this work. J.V.: does not have any perceived or actual conflicts of interest relevant to this work. K.M.K.: is employed by C2N Diagnostics and owns equity shares in C2N Diagnostics. S.E.B.: Contract Research: GE Healthcare, Genentech, Optina, Roche, Eli Lilly, Eisa/Biogen Idec, NovoNordisk, Lilly Avid. Payments made to Institution. No personal investigator fees taken including Eli Lilly. Peer Reviewed: Ontario Brain Institute, CIHR, Leducq Foundation, Heart and Stroke Foundation of Canada, NIH, Alzheimer's Drug Discovery Foundation, Brain Canada, Weston Brain Institute, Canadian Partnership for Stroke Recovery, Canadian Foundation for Innovation, Focused Ultrasound Foundation, Alzheimer's Association US, Department of National Defence, Montreal Medical International Kuwait, Queen's University, Compute Canada Resources for Research Groups, CANARIE, Networks of Centres of Excellence of Canada. Payments made to Institution. No personal investigator fees taken. Consulting Fees: Roche, Biogen, Eli Lilly, NovoNordisk, Eisai. Payments made to me. Honoraria: Biogen, Roche Models of Care Analysis in Canada, and Eisai MRI Workshop. Payments made to me. M.D.H.: Consulting fees: Sun Pharma, Brainsgate Inc (paid work for adjudication of clinical trial outcomes); Grants/Contracts: ESCAPE‐NA1 and ESCAPE NEXT trials (NoNO Inc. CIHR), ESCAPE MeVO study (Medtronic); TEMPO‐2 trial (CIHR, Heart & Stroke Foundation of Canada, Boehringer‐Ingelheim). Consulting Fees: Sun Pharmam Brainsgate Inc (paid work for adjudication of clinical trial outcomes). Stock or stock options: Circle Inc. Leadership or fiduciary role: President (Canadian Neurological Sciences Federation (not for profit), Canadian Stroke Consortium (not for profit). Data Safety Monitoring Board activity: DSMC Chair (DUMAS trial, Oncovir Hiltonel trial) and DSMB member (ARTESIA trial, BRAIN‐AF trial, LAAOS‐4 trial). R.C.: Grants: CIHR, Canadian Consortium on Neurodegeneration of Aging and Compass ND/CIHR; Sparx3/NIH, Synergic‐2 Clinical Trial (Weston Foundation to University of Alberta via Western University). Monitoring Board activity: Amborxal Trial (unpaid scientific advisor) and Parkinson Canada (unpaid research and clinical advisory board). C.L.W.: does not have any perceived or actual conflicts of interest relevant to this work. E.E.S.: has previously served on a steering committee (unpaid) for Alnylam Pharmaceuticals and on advisory boards (unpaid) for Eisai and Eli Lilly. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Dot plots of plasma concentrations of Aβ40, Aβ42, and the Aβ42/40 ratio quantified through IPMS (A‐C) and Simoa (D‐F) in healthy controls and CAA. Aβ, beta‐amyloid; CAA, cerebral amyloid angiopathy; IPMS, immunoprecipitation liquid chromatography mass‐spectrometry; Simoa, single molecule array.
FIGURE 2
FIGURE 2
Dot plots of plasma concentrations of (A) p‐tau‐181, (B) NfL, and (C) GFAP quantified through Simoa in healthy controls and CAA. CAA, cerebral amyloid angiopathy; GFAP, glial fibrillary acidic protein; NfL, neurofilament light chain.
FIGURE 3
FIGURE 3
AUCs for Simoa plasma (A) Aβ42/40, p‐tau‐181, NfL, and GFAP individually and (B) in combination. Aβ, beta‐amyloid; AUC, total area under the receiver operating characteristic curve; GFAP, glial fibrillary acidic protein; NfL, neurofilament light chain; Simoa, single molecule array.
See this image and copyright information in PMC

References

    1. Quereshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373:1632‐1644. - PMC - PubMed
    1. Jolink WM KC, Brouwers PJ, Kappelle LJ, Vaartjes I. Time trends in incidence, case fatality, and mortality of intracerebral hemorrhage. Neurology. 2015;85:1318‐1324. - PubMed
    1. Sheth KN. Spontaneous intracerebral hemorrhage. N Engl J Med. 2022;387:1589‐1596. - PubMed
    1. Charidimou A, Boulouis G, Frosch MP, et al. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study. The Lancet Neurology. 2022;21:714‐725. - PMC - PubMed
    1. Boyle PA, Yu L, Leurgans SE, et al. Attributable risk of Alzheimer's dementia attributed to age‐related neuropathologies. Ann Neurol. 2019;85:114‐124. - PMC - PubMed

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