期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms20194674
关键词
VGF; cerebrospinal fluid; dementia with Lewy bodies; synaptic dysfunction
资金
- Stichting Alzheimer Nederland
- Stichting VUmc fonds
- Stichting Dioraphte
- Memorabel grant programme of the Netherlands Organisation of Health Research and Development (ZonMW) [733050509, 733050102]
- German Federal Ministry of Education and Research [FTLDc 01GI1007A]
- EU Joint Programme-Neurodegenerative Disease networks PreFRontAls [01ED1512]
- foundation of the state of Baden-Wuerttemberg
- German science foundation (DFG) [SFB 1237]
- Regione Sardegna, Italy Fundamental and Basic research grant [2012-CRP-60834]
In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer's disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and alpha-synuclein (0.55 < r < 0.75), but not with A beta 1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.
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