Altered CSF orexin and α-synuclein levels in dementia patients

Molecular Memory Research Unit, The Wallenberg Laboratory, Skåne University Hospital (SUS) Malmö, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 12/2011; 29(1):125-32. DOI: 10.3233/JAD-2012-111655
Source: PubMed


Neurodegenerative dementia, most frequently represented by Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), is often accompanied by altered sleeping patterns and excessive daytime sleepiness. Studies showing an association between the neuropeptide orexin and AD/DLB-related processes such as amyloid-β (Aβ)1-42 plaque formation, α-synuclein accumulation and inflammation indicate that orexin might play a pathogenic role similar to the situation in narcolepsy. Our study of patients with AD (n = 26), DLB (n = 18), and non-demented controls (n = 24) shows a decrease in cerebrospinal fluid (CSF) orexin concentrations in DLB versus AD patients and controls. The observed differences in orexin levels were found to be specific to female DLB patients. We also show that the female DLB patients exclusively displayed lower levels of α-synuclein compared to AD patients and controls. Orexin was linked to α-synuclein and total-tau in female non-demented controls whereas associations between orexin and Aβ1-42 concentrations were absent in all groups regardless of gender. Thus, the proposed links between orexin, Aβ, and α-synuclein pathology could not be monitored in CSF protein concentrations. Interestingly, α-synuclein was strongly correlated to the CSF levels of total-Tau in all groups, suggesting α-synuclein to be an unspecific marker of neurodegeneration. We conclude that lower levels of CSF orexin are specific to DLB versus AD and appear unrelated to Aβ1-42 and α-synuclein levels in AD and DLB. Alterations in CSF orexin and α-synuclein levels may be related to gender which warrants further investigation.

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    • ") (Brownell and Conti 2010) @BULLETCell loss (Fronczek et al. 2012) @BULLETCell loss (Thannickal et al. 2007) (Lessig et al. 2010) @BULLETDecreased plasma orexin concentration (Çoban et al. 2013) @BULLETLoss of fibers (Stanley and Fadel 2012)(Downs et al. 2007) (Zhang et al. 2005) @BULLETDecreased CSF orexin concentration (Fronczek et al. 2012) @BULLETLewy Bodies (Fronczek et al. 2007) @BULLETDecreased CSF orexin concentration in DLB (Wennström et al. 2012) @BULLETDecreased responsiveness to orexin in projection areas (Stanley and Fadel 2012) Noradrenergic Locus Coeruleus (LC) @BULLETDecreased noradrenaline reuptake at terminals (Shores et al. 1999)(Zhu et al. 2005)(Shirokawa et al. 2003) @BULLETCell loss (Brunnström et al. 2011) @BULLETCell loss (Brunnström et al. 2011) @BULLETLoss of neuron pigmentation (Hoogendijk et al. 1995) @BULLETCell loss (Brunnström et al. 2011) @BULLETDecreased DBH (Zhu et al. 2005) @BULLETNFTs (Grudzien et al. 2007) @BULLETLewy Bodies (Seidel et al. 2014) @BULLETIntracellular inclusion bodies (Iwanaga et al. 1997) @BULLETIncreased CHOP (Naidoo et al. 2011) "
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