期刊
出版社
WILEY
DOI: 10.1002/dad2.12296
关键词
Alzheimer's disease; amyloid beta; blood-brain barrier; cerebrospinal fluid; subcortical small-vessel disease
资金
- Swedish government
- Swedish county councils
- ALF agreement [ALFGBG-724331, ALFGBG-722371, ALFGBG-720931, ALFGBG-715986, ALFGBG-720661]
- Swedish Alzheimer Foundation
- Demensfonden, Sweden
- Gun & Bertil Stohnes Stiftelse, Sweden
- Stiftelsen for Gamla Tjanarinnor, Sweden
- Gunvor och Josef Aners stiftelse, Sweden
- Formas, a Swedish government research council
- Hedlunds stiftelse, Sweden
- Stiftelsen Hjalmar Svenssons Forskningsfond, Sweden
- Stiftelsen Langmanska kulturfonden, Sweden
- Magnus Bergvalls Stiftelse, Sweden
- Stiftelsen Psykiatriska Forskningsfonden, Sweden
- Royal Society of Arts and Sciences in Gothenburg, Sweden
- Sweden's innovation agency Vinnova
- Wenner-Gren Foundations, Sweden
- Wilhelm & Martina Lundgrens Vetenskapsfond, Sweden
- Ahlenstiftelsen, Sweden
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Sweden
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Alzheimer DrugDiscovery Foundation (ADDF), USA [201809-2016862]
- AD Strategic Fund
- Alzheimer's Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- Olav Thon Foundation
- Erling-Persson Family Foundation
- Stiftelsen for Gamla Tjanarinnor
- Hjarnfonden, Sweden [FO2019-0228, FO2017-0243]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]
- UK Dementia Research Institute at UCL
- Alzheimer Drug Discovery Foundation (ADDF), USA [RDAPB-201809-2016615]
- Swedish Alzheimer Foundation [AF-742881]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- National Institutes of Health (NIH), USA [1R01AG068398-01]
- Alzheimer's Association 2021 Zenith Award [ZEN-21-848495]
SSVD patients exhibit distinct biomarker profiles from AD and mixed AD/SSVD, with lower sAPP-β levels and blood-brain barrier dysfunction suggesting possible diagnostic tools for SSVD.
Introduction Subcortical small-vessel disease (SSVD) is the most common vascular cognitive disorder. However, because no disease-specific cerebrospinal fluid (CSF) biomarkers are available for SSVD, our aim was to identify such markers. Methods We included 170 healthy controls and patients from the Gothenburg Mild Cognitive Impairment (MCI) study clinically diagnosed with SSVD dementia, Alzheimer's disease (AD), or mixed AD/SSVD. We quantified CSF levels of amyloid-beta (A beta)(x-38), A beta(x-40), A beta(x-42), as well as soluble amyloid precursor protein (sAPP)-alpha and sAPP-beta. Results sAPP-beta was lower in SSVD patients than in AD patients and controls. Receiver-operating characteristic (ROC) analyses showed that sAPP-beta moderately separated SSVD from AD and controls. Moreover, the CSF/serum albumin ratio was elevated exclusively in SSVD and could moderately separate SSVD from the other groups in ROC analyses. Discussion SSVD has a biomarker profile that differs from that of AD and controls, and to some extent also from mixed AD/SSVD, suggesting that signs of blood-brain barrier (BBB) dysfunction and sAPP-beta could be additional tools to diagnose SSVD. Highlights Patients with subcortical small-vessel disease (SSVD) exhibited reduced levels of sAPP-beta and disturbances of the blood-brain barrier (BBB). This biochemical pattern is different from that of Alzheimer's disease (AD) and to some degree from that of mixed AD/SSVD. Our findings are speaking in favor of the concept that SSVD is a distinct vascular cognitive disorder (VCD) form.
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