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dc.contributor.authorMcAleese, Kirsty E.
dc.contributor.authorGraham, Sophie
dc.contributor.authorDey, Madhurima
dc.contributor.authorWalker, Lauren
dc.contributor.authorErskine, Daniel
dc.contributor.authorJohnson, Mary
dc.contributor.authorJohnston, Eleanor
dc.contributor.authorThomas, Alan J.
dc.contributor.authorMcKeith, Ian G.
dc.contributor.authorDeCarli, Charles
dc.contributor.authorAttems, Johannes
dc.identifier.citationMcAleese , K E , Graham , S , Dey , M , Walker , L , Erskine , D , Johnson , M , Johnston , E , Thomas , A J , McKeith , I G , DeCarli , C & Attems , J 2019 , ' Extravascular fibrinogen in the white matter of Alzheimer's disease and normal aged brains : implications for fibrinogen as a biomarker for Alzheimer's disease ' , Brain Pathology , vol. 29 , no. 3 , pp. 414-424 .
dc.identifier.otherPURE: 256767610
dc.identifier.otherPURE UUID: bcd2b324-71d5-4f47-b15c-1b59cb5f4878
dc.identifier.otherRIS: urn:A7216E4CE03A4DBC81EC6FF16B4EB7AF
dc.identifier.otherScopus: 85060754294
dc.identifier.otherWOS: 000465432300009
dc.descriptionThe research was supported by the Alzheimer’s Society (grant numbers AS-PG-2013-011 and AS-JF-18-01). Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK.en
dc.description.abstractThe blood‐brain barrier (BBB) regulates cerebrovascular permeability and leakage of blood‐derived fibrinogen has been associated with cerebral arteriolosclerosis small vessel disease (SVD) and subsequent white matter lesions (WML). Furthermore, BBB‐dysfunction is associated with the pathogenesis of Alzheimer's disease (AD) with the presence of CSF plasma proteins suggested to be a potential biomarker of AD. We aimed to determine if extravascular fibrinogen in the white matter was associated with the development of AD hallmark pathologies, i.e., hyperphosphorylated tau (HPτ) and amyloid‐β (Aβ), SVD, cerebral amyloid angiopathy (CAA) and measures of white matter damage. Using human post‐mortem brains, parietal tissue from 20 AD and 22 non‐demented controls was quantitatively assessed for HPτ, Aβ, white matter damage severity, axonal density, demyelination and the burden of extravascular fibrinogen in both WML and normal appearing white matter (NAWM). SVD severity was determined by calculating sclerotic indices. WML‐ and NAWM fibrinogen burden was not significantly different between AD and controls nor was it associated with the burden of HPτ or Aβ pathology, or any measures of white matter damage. Increasing severity of SVD was associated with and a predictor (both p < 0.05) of both higher WML‐ and NAWM fibrinogen burden (both P<0.05) in controls only. In cases with minimal SVD NAWM fibrinogen burden was significantly higher in the AD cases (p<0.05). BBB dysfunction was present in both non‐demented and AD brains and was not associated with the burden of AD‐associated cortical pathologies. BBB dysfunction was strongly associated with SVD but only in the non‐demented controls. In cases with minimal SVD, BBB dysfunction was significantly worse in AD cases possibly indicating the influence of CAA. In conclusions, extravascular fibrinogen is not associated with AD hallmark pathologies but indicates SVD, suggesting that the presence of fibrinogen in the CSF is not a surrogate marker for AD pathology.
dc.relation.ispartofBrain Pathologyen
dc.rightsCopyright © 2018 International Society of Neuropathology. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectBlood-brain barrieren
dc.subjectAlzheimer's diseaseen
dc.subjectCerebral small vessel diseaseen
dc.subjectWhite matter lesionen
dc.subjectWhite matter hyperintensitiesen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.titleExtravascular fibrinogen in the white matter of Alzheimer's disease and normal aged brains : implications for fibrinogen as a biomarker for Alzheimer's diseaseen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.description.statusPeer revieweden

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