Journal
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
Volume 14, Issue 1, Pages -Publisher
WILEY
DOI: 10.1002/dad2.12296
Keywords
Alzheimer's disease; amyloid beta; blood-brain barrier; cerebrospinal fluid; subcortical small-vessel disease
Categories
Funding
- Swedish government [ALFGBG-724331, ALFGBG-722371, ALFGBG-720931, ALFGBG-715986, ALFGBG-720661]
- Swedish county councils, and the ALF agreement [ALFGBG-724331, ALFGBG-722371, ALFGBG-720931, ALFGBG-715986, ALFGBG-720661]
- Swedish Alzheimer Foundation
- Demensfonden, Sweden
- Gun amp
- Bertil Stohnes Stiftelse, Sweden
- Stiftelsen foer Gamla Tjaenarinnor, Sweden
- Gunvor och Josef Aners stiftelse, Sweden
- Formas, a Swedish government research council for sustainable development
- Hedlunds stiftelse, Sweden
- Stiftelsen Hjalmar Svenssons Forskningsfond, Sweden
- Stiftelsen Laengmanska kulturfonden, Sweden
- Magnus Bergvalls Stiftelse, Sweden
- Stiftelsen Psykiatriska Forskningsfonden, Sweden
- Royal Society of Arts and Sciences in Gothenburg, Sweden
- Sweden's innovation agency Vinnova
- The Wenner-Gren Foundations, Sweden
- Wilhelm amp
- Martina Lundgrens Vetenskapsfond, Sweden
- ahlenstiftelsen, Sweden
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Sweden
- Swedish Research Council [2018-02532]
- European Research Council [681712]
- Alzheimer Drug Discovery 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 foer Gamla Tjaenarinnor
- Hjaernfonden, Sweden [FO2019-0228]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]
- UK Dementia Research Institute at UCL
- National Institutes of Health (NIH), USA [1R01AG068398-01]
- Alzheimer's Association 2021 Zenith Award [ZEN-21-848495]
Ask authors/readers for more resources
We found that SSVD patients have a different biomarker profile, with lower levels of sAPP-β compared to AD patients and controls. We also observed signs of blood-brain barrier dysfunction in SSVD. These findings support the concept that SSVD is a distinct form of vascular cognitive disorder (VCD).
IntroductionSubcortical 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. MethodsWe 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. ResultssAPP-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. DiscussionSSVD 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. HighlightsPatients 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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