Clusterin in cerebrospinal fluid: Analysis of carbohydrates and quantification of native and glycosylated forms

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Nilselid, A.-M.Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Institute of Clinical Neuroscience, The Sahlgrenska Academy, Göteborg University, Se, 431 80 Mölndal, Sweden,Neurotech Department, Section of Clinical Geriatrics, Memoryclinic M 51, Huddinge, SE-141 86 Stockholm, Sweden (author)

Clusterin in cerebrospinal fluid : Analysis of carbohydrates and quantification of native and glycosylated forms

Article/chapterEnglish2006

Publisher, publication year, extent ...

Elsevier BV,2006
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LIBRIS-ID:oai:DiVA.org:liu-50213
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-50213URI
https://doi.org/10.1016/j.neuint.2005.12.005DOI
https://gup.ub.gu.se/publication/36097URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:1942162URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Clusterin is suggested to be involved in the pathogenesis of Alzheimer's disease. Clusterin expression is increased in brain tissue in affected regions of Alzheimer patients, and intense clusterin staining is found in both senile plaques and in neuronal and glia cells. In contrast, the cerebrospinal fluid level of clusterin in Alzheimer patients has, thus far, been found unchanged. Clusterin is a glycosylated protein, and an alteration of its glycosylation in Alzheimer's disease might influence accurate quantification in cerebrospinal fluid through interference of antibody binding to the protein. Using enzymatic deglycosylation of clusterin isolated from cerebrospinal fluid, we found that the carbohydrates attached to clusterin were of the N-linked type and sialic acids. Based on this finding, cerebrospinal fluid samples from Alzheimer patients (n = 99) and controls (n = 39) were analysed. The samples were treated with peptide: N-glycanase F, cleaving off N-linked carbohydrates, and clusterin was quantified before and after deglycosylation using a new sandwich enzyme-linked immunosorbent assay. Clusterin was significantly increased in Alzheimer patients, in both native (7.17 ± 2.43 AU versus 5.73 ± 2.09 AU, p = 0.002), and deglycosylated samples (12.19 ± 5.00 AU versus 9.68 ± 4.38 AU, p = 0.004). Deglycosylation led to increased measured levels of clusterin by 70% (p < 0.001) in Alzheimer patients and 67% (p < 0.001) in controls. These findings indicate that glycosylation of proteins may interfere with their quantification. The results show that clusterin is significantly increased in cerebrospinal fluid from Alzheimer patients as a group, supporting that clusterin might be involved in the pathogenesis of Alzheimer's disease. However, the individual clusterin levels overlap between the two groups, and thus cerebrospinal fluid clusterin measurement is not suitable as a biochemical marker in the diagnosis of Alzheimer's disease. © 2006 Elsevier Ltd. All rights reserved.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Alzheimer's disease
Carbohydrates
Cerebrospinal fluid
NATURAL SCIENCES
NATURVETENSKAP
Cerebrospinal fluid; Carbohydrates; Alzheimer's disease

Added entries (persons, corporate bodies, meetings, titles ...)

Davidsson, Pia,1962Discovery Medicine, Molecular Sciences AstraZeneca, Mölndal, Sweden(Swepub:gu)xdavpi (author)
Nagga, K.Östergötlands Läns Landsting,Geriatriska kliniken (author)
Andreasen, N.Neurotech Department, Section of Clinical Geriatrics, Memoryclinic M 51, Huddinge, SE-141 86 Stockholm, Sweden (author)
Fredman, Pam,1950Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Institute of Clinical Neuroscience, The Sahlgrenska Academy, Göteborg University, Se, 431 80 Mölndal, Sweden(Swepub:gu)xfredp (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Institute of Clinical Neuroscience, The Sahlgrenska Academy, Göteborg University, Se, 431 80 Mölndal, Sweden(Swepub:gu)xbleka (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

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In:Neurochemistry International: Elsevier BV48:8, s. 718-280197-01861872-9754
In:Neurochem Int.: Elsevier BV48:8, s. 718-28

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