@article{d6aefa2c46d2442ea369a58aa8b58568,
title = "Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy",
abstract = "Aims: We investigated the potential of apolipoprotein D (apoD) as cerebrospinal fluid (CSF) biomarker for cerebral amyloid angiopathy (CAA) after confirmation of its association with CAA pathology in human brain tissue. Methods: The association of apoD with CAA pathology was analysed in human occipital lobe tissue of CAA (n = 9), Alzheimer{\textquoteright}s disease (AD) (n = 11) and healthy control cases (n = 11). ApoD levels were quantified in an age- and sex-matched CSF cohort of CAA patients (n = 31), AD patients (n = 27) and non-neurological controls (n = 67). The effects of confounding factors (age, sex, serum levels) on apoD levels were studied using CSF of non-neurological controls (age range 16–85 years), and paired CSF and serum samples. Results: ApoD was strongly associated with amyloid deposits in vessels, but not with parenchymal plaques in human brain tissue. CSF apoD levels correlated with age and were higher in men than women in subjects >50 years. The apoD CSF/serum ratio correlated with the albumin ratio. When controlling for confounding factors, CSF apoD levels were significantly lower in CAA patients compared with controls and compared with AD patients (P = 0.0008). Conclusions: Our data show that apoD is specifically associated with CAA pathology and may be a CSF biomarker for CAA, but clinical application is complicated due to dependency on age, sex and blood–CSF barrier integrity. Well-controlled follow-up studies are required to determine whether apoD can be used as reliable biomarker for CAA.",
keywords = "Alzheimer disease, amyloid, apolipoprotein D, biomarkers, blood–CSF barrier, cerebral amyloid angiopathy, cerebrospinal fluid, blood-CSF barrier",
author = "Kuiperij, \{H. B.\} and Hondius, \{D. C.\} and I. Kersten and Versleijen, \{A. A.M.\} and Rozemuller, \{A. J.M.\} and Greenberg, \{S. M.\} and Schreuder, \{F. H.B.M.\} and Klijn, \{C. J.M.\} and Verbeek, \{M. M.\}",
note = "Funding Information: This study was part of the CAVIA (no. 733050202) and the BIONIC projects (no. 733050822), which have been made possible by ZonMW. These projects are part of {\textquoteleft}Memorabel{\textquoteright}, the research and innovation program for dementia, as part of the Dutch national {\textquoteleft}Deltaplan for Dementia{\textquoteright}: zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADX Neurosciences, Philips Healthcare, Stony Brook University and Massachusetts General Hospital. The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University. CJM Klijn and FHBM Schreuder are supported by a clinical established investigator grant of the Dutch Heart Foundation (grant 2012T077) and CJM Klijn by an ASPASIA grant from The Netherlands Organization for Health Research and Development, ZonMW (grant 015008048). Funding information: Funding Information: This study was part of the CAVIA (no. 733050202) and the BIONIC projects (no. 733050822), which have been made possible by ZonMW. These projects are part of {\textquoteleft}Memorabel{\textquoteright}, the research and innovation program for dementia, as part of the Dutch national {\textquoteleft}Deltaplan for Dementia{\textquoteright}: zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADX Neurosciences, Philips Healthcare, Stony Brook University and Massachusetts General Hospital. The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University. CJM Klijn and FHBM Schreuder are supported by a clinical established investigator grant of the Dutch Heart Foundation (grant 2012T077) and CJM Klijn by an ASPASIA grant from The Netherlands Organization for Health Research and Development, ZonMW (grant 015008048). HBK and MMV designed the study. DCH, IK and AAMV performed experiments. HBK, DCH, AJMR and MMV analysed and/or interpreted data. AJMR, SMG, FHBMS and CJMK contributed to the acquisition of patient data and samples. HBK drafted the manuscript. All authors critically revised the manuscript. Funding Information: This study was part of the CAVIA (no. 733050202) and the BIONIC projects (no. 733050822), which have been made possible by ZonMW. These projects are part of {\textquoteleft}Memorabel{\textquoteright}, the research and innovation program for dementia, as part of the Dutch national {\textquoteleft}Deltaplan for Dementia{\textquoteright}: zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADX Neurosciences, Philips Healthcare, Stony Brook University and Massachusetts General Hospital. The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University. CJM Klijn and FHBM Schreuder are supported by a clinical established investigator grant of the Dutch Heart Foundation (grant 2012T077) and CJM Klijn by an ASPASIA grant from The Netherlands Organization for Health Research and Development, ZonMW (grant 015008048). Publisher Copyright: {\textcopyright} 2019 The Authors. Neuropathology and Applied Neurobiology published by John Wiley \& Sons Ltd on behalf of British Neuropathological Society",
year = "2020",
month = aug,
doi = "10.1111/nan.12595",
language = "English",
volume = "46",
pages = "431--440",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",
}