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Altered CSF Orexin and α-Synuclein Levels in Dementia Patients.

Wennström, Malin LU ; Londos, Elisabet LU ; Minthon, Lennart LU and Nielsen, Henrietta LU (2012) In Journal of Alzheimer's Disease 29(1). p.125-132
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bodies, orexin, biomarker, dementia with Lewy, Alzheimer's disease, Alpha-synuclein
in
Journal of Alzheimer's Disease
volume
29
issue
1
pages
125 - 132
publisher
IOS Press
external identifiers
  • wos:000301139000011
  • pmid:22207004
  • scopus:84858136734
ISSN
1387-2877
DOI
10.3233/JAD-2012-111655
language
English
LU publication?
yes
id
db0140b3-22f3-4833-87c7-420799f842c7 (old id 2273457)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22207004?dopt=Abstract
date added to LUP
2012-01-03 16:19:22
date last changed
2017-09-10 03:06:57
@article{db0140b3-22f3-4833-87c7-420799f842c7,
  abstract     = {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.},
  author       = {Wennström, Malin and Londos, Elisabet and Minthon, Lennart and Nielsen, Henrietta},
  issn         = {1387-2877},
  keyword      = {bodies,orexin,biomarker,dementia with Lewy,Alzheimer's disease,Alpha-synuclein},
  language     = {eng},
  number       = {1},
  pages        = {125--132},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Altered CSF Orexin and α-Synuclein Levels in Dementia Patients.},
  url          = {http://dx.doi.org/10.3233/JAD-2012-111655},
  volume       = {29},
  year         = {2012},
}