Characterizing Plasma Biomarkers of Cerebral Amyloid Angiopathy

Muir, Ryan Thomas

Characterizing Plasma Biomarkers of Cerebral Amyloid Angiopathy

dc.contributor.advisor	Smith, Eric E.
dc.contributor.author	Muir, Ryan Thomas
dc.contributor.committeemember	Hill, Michael D.
dc.contributor.committeemember	Black, Sandra E.
dc.contributor.committeemember	Hsuing, Robin
dc.date.accessioned	2024-08-01T15:44:09Z
dc.date.available	2024-08-01T15:44:09Z
dc.date.issued	2024-07-26
dc.description.abstract	BACKGROUND: Cerebral Amyloid Angiopathy (CAA) is characterized by the progressive deposition of beta-amyloid in cortical and leptomeningeal small vessels leading to hemorrhagic stroke and dementia. While CAA is diagnosed using Boston Criteria 2.0, they are not always possible to apply. Plasma biomarkers (Aβ42, Aβ40, phosphorylated-tau (p-tau), neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP)) might improve diagnostic accuracy. This study evaluates whether plasma biomarkers: (i) differ in CAA compared to controls (ii) discriminate a diagnosis of CAA individually and in combination and (iii) are associated with cognition and neuroimaging biomarkers. METHODS: Data are from a multi-centre cohort study of participants with probable CAA and healthy controls. Participants had plasma collected and underwent neurocognitive evaluation and magnetic resonance imaging. Aβ was quantified with two independent methods: immunoprecipitation mass-spectrometry (IPMS) and single molecule array assay (Simoa). Plasma p-tau181, NfL and GFAP were quantified with Simoa. Neuroimaging biomarkers of small vessel disease, atrophy, white matter integrity and cerebrovascular reactivity (CVR) were quantified. Logistic regression was used to compute areas under the receiver operating characteristic curve (AUC) to assess biomarker discriminative performance of ascertaining a diagnosis of CAA. Associations between plasma biomarkers, cognition and neuroimaging biomarkers were evaluated with generalized linear models. RESULTS: 45 participants with CAA and 47 controls were eligible. With both methods, the Aβ42/40 ratio was reduced in CAA compared to controls. Furthermore, those with CAA had elevated p-tau181 and NfL. A combination of Aβ42/40 (Simoa), p-tau181, and NfL resulted in an AUC of 0.90. Reduced Aβ42/40 was associated with poorer speed of processing. Increasing NfL was associated with reduced Montreal Cognitive Assessment Scores, lower CVR and increasing CAA severity. CONCLUSIONS: This study identified differences in plasma Aβ42/40, p-tau181 and NfL in CAA compared and provides evidence that a panel of these biomarkers can achieve excellent diagnostic discriminability. This study also demonstrates that a marker of cerebral amyloidosis (Aβ42/40) is associated with speed of processing difficulties in those with CAA, while NfL was associated with global cognition, CAA severity and CVR. Overall, plasma biomarkers might, in future, help improve the evaluation and detection of CAA.
dc.identifier.citation	Muir, R. T. (2024). Characterizing plasma biomarkers of cerebral amyloid angiopathy (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/119260
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Cerebral Amyloid Angiopathy
dc.subject	Hemorrhagic Stroke
dc.subject	Plasma Biomarkers
dc.subject	Cerebral Small Vessel Disease
dc.subject.classification	Medicine and Surgery
dc.subject.classification	Epidemiology
dc.title	Characterizing Plasma Biomarkers of Cerebral Amyloid Angiopathy
dc.type	master thesis
thesis.degree.discipline	Medicine – Community Health Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.