Blood‐brain barrier dysfunction and reduced cerebrospinal fluid levels of soluble amyloid precursor protein‐β in patients with subcortical small‐vessel disease
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Medientyp:
E-Artikel
Titel:
Blood‐brain barrier dysfunction and reduced cerebrospinal fluid levels of soluble amyloid precursor protein‐β in patients with subcortical small‐vessel disease
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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‐β (Aβ)<jats:sub>x‐38</jats:sub>, Aβ<jats:sub>x‐40</jats:sub>, Aβ<jats:sub>x‐42</jats:sub>, as well as soluble amyloid precursor protein (sAPP)‐α and sAPP‐β.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>sAPP‐β was lower in SSVD patients than in AD patients and controls. Receiver‐operating characteristic (ROC) analyses showed that sAPP‐β 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.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>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‐β could be additional tools to diagnose SSVD.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet">
<jats:list-item><jats:p>Patients with subcortical small‐vessel disease (SSVD) exhibited reduced levels of sAPP‐β and disturbances of the blood‐brain barrier (BBB).</jats:p></jats:list-item>
<jats:list-item><jats:p>This biochemical pattern is different from that of Alzheimer's disease (AD) and to some degree from that of mixed AD/SSVD.</jats:p></jats:list-item>
<jats:list-item><jats:p>Our findings are speaking in favor of the concept that SSVD is a distinct vascular cognitive disorder (VCD) form.</jats:p></jats:list-item></jats:list></jats:p></jats:sec>