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Cystatin C Levels are Positively Correlated with both Aβ42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.ORCID iD: 0000-0003-2247-8454
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2010 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 21, no 2, 471-478 p.Article in journal (Refereed) Published
Abstract [en]

Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (Abeta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Abeta42, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Abeta42, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Abeta42, and tau levels across disease groups were investigated. Cystatin C, Abeta42, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Abeta and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 mumol/L +/- 1.7), MCI (5.4 mumol/L +/- 1.48), and controls (5.6 mumol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61-0.81, p< 0.0001) and Abeta42 (r=0.35-0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Abeta42 levels in CSF independent of age, gender, and APOE genotype.

Place, publisher, year, edition, pages
2010. Vol. 21, no 2, 471-478 p.
Keyword [en]
Alzheimer's disease, biomarkers, case control study, cystatin C, epidemiology, risk factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-130132DOI: 10.3233/JAD-2010-091594ISI: 000281887600013PubMedID: 20555147OAI: oai:DiVA.org:uu-130132DiVA: diva2:357157
Available from: 2010-10-15 Created: 2010-09-01 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Amyloid β-protein, Cystatin C and Cathepsin B as Biomarkers of Alzheimer's Disease
Open this publication in new window or tab >>Amyloid β-protein, Cystatin C and Cathepsin B as Biomarkers of Alzheimer's Disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It is suggested that Alzheimer’s disease (AD) is caused by an imbalance between production, degradation and clearance of the amyloid-β (Aβ) protein. This imbalance leads to aggregation of Aβ and tau proteins and neurodegeneration in the brain. Today there is increasing evidence that the balance between the protease cathepsin B and the protease inhibitor cystatin C affects the tendency for Aβ to aggregate. The primary aim of this thesis was to investigate Aβ, cystatin C and cathepsin B levels in blood and cerebro-spinal fluid (CSF) in relation to the risk of AD.

Studies I & II were based on the re-examinations of participants, at ages 70 and 77, in the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based prospective study initiated in 1970 (participants then being 50 years of age). In ULSAM, low plasma Aβ1-40 (Study I) and low serum cystatin C levels (Study II) were associated with a higher risk of AD. Studies III & IV were based on a cross-sectional sample of people with AD, mild cognitive impairment and healthy controls, recruited at three Swedish Memory Disorder units: Uppsala University Hospital, Uppsala, Skåne University Hospital, Malmö, and Karolinska University Hospital, Huddinge, Stockholm. In Study III, CSF cystatin C levels were positively correlated with both Aβ1-42 and tau levels. In Study IV, individuals with AD had higher mean plasma cathepsin B levels than healthy controls.

In conclusion, low plasma Aβ1-40 and low serum cystatin C levels may precede clinically manifest AD in elderly men, cystatin C levels are positively correlated with Aβ1-42 and tau levels in CSF, and mean plasma cathepsin B levels are higher in people with AD compared to healthy controls. In addition to Aβ1-42 and tau levels in CSF, Aβ1-40, cystatin C and cathepsin B levels in blood may reflect the risk of AD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 626
Keyword
Alzheimer´s disease, amyloid β-protein, cystatin C, cathepsin B, biomarkers, risk factors, epidemiology
National Category
Geriatrics
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-132175 (URN)978-91-554-7956-5 (ISBN)
Public defence
2011-01-20, Enghoffsalen, Ing. 50, bv, Akademiska sjukhuset, Uppsala, 13:00 (English)
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Available from: 2010-12-20 Created: 2010-10-15 Last updated: 2017-01-25Bibliographically approved

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Sundelöf, JohanSundstrom, JohanLarsson, AndersIngelsson, MartinBasun, HansLannfelt, Lars

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