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Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia

Nilsson, Carol L. LU ; Brinkmalm, A; Minthon, Lennart LU ; Blennow, K and Ekman, R (2001) In Peptides 22(12). p.2105-2112
Abstract
Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing,... (More)
Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Peptides
volume
22
issue
12
pages
2105 - 2112
publisher
Elsevier
external identifiers
  • wos:000173304800022
  • scopus:0035747677
ISSN
1873-5169
DOI
10.1016/S0196-9781(01)00571-X
language
English
LU publication?
no
id
31b72ebd-8ab7-4a85-9373-6019303f8002 (old id 1297244)
date added to LUP
2009-07-15 09:46:59
date last changed
2018-08-05 03:35:09
@article{31b72ebd-8ab7-4a85-9373-6019303f8002,
  abstract     = {Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states.},
  author       = {Nilsson, Carol L. and Brinkmalm, A and Minthon, Lennart and Blennow, K and Ekman, R},
  issn         = {1873-5169},
  language     = {eng},
  number       = {12},
  pages        = {2105--2112},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia},
  url          = {http://dx.doi.org/10.1016/S0196-9781(01)00571-X},
  volume       = {22},
  year         = {2001},
}