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Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men: A Prospective, Population-Based Cohort Study
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 Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.ORCID iD: 0000-0003-2247-8454
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2008 (English)In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 65, no 2, 256-63 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Beta amyloid (Abeta) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma. OBJECTIVE: To examine plasma levels of Abeta peptides Abeta(40) and Abeta(42) as predictors of incident AD and other types of dementia. DESIGN: Prospective, population-based cohort study. SETTING: The Uppsala Longitudinal Study of Adult Men. PARTICIPANTS: Plasma Abeta(40) and Abeta(42) levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review. MAIN OUTCOME MEASURES: Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma Abeta(40) and Abeta(42). RESULTS: From the age of 77 years at baseline, 46 individuals developed AD at follow-up (median, 5.3 years). A low plasma Abeta(40) level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest Abeta(40) tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 individuals developed AD. Plasma Abeta(40) and Abeta(42) levels measured at age 70 years were not significantly associated with incident AD. CONCLUSIONS: Low plasma Abeta(40) levels predicted incident AD in elderly men independently of potential confounders. Plasma Abeta(42) levels were not significantly associated with AD incidence. The clinical value of Abeta measurement in plasma remains to be established in future studies.

Place, publisher, year, edition, pages
2008. Vol. 65, no 2, 256-63 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-15781DOI: 10.1001/archneurol.2007.57ISI: 000253058800015PubMedID: 18268197OAI: oai:DiVA.org:uu-15781DiVA: diva2:43552
Available from: 2008-03-05 Created: 2008-03-05 Last updated: 2017-12-08Bibliographically 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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Supervisors
Available from: 2010-12-20 Created: 2010-10-15 Last updated: 2017-01-25Bibliographically approved

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Sundelöf, JohanGiedraitis, VilmantasSundström, JohanIngelsson, ErikRönnemaa, ElinaGunnarsson, Malin DegermanBasun, HansIngelsson, MartinLannfelt, LarsKilander, Lena

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Sundelöf, JohanGiedraitis, VilmantasSundström, JohanIngelsson, ErikRönnemaa, ElinaGunnarsson, Malin DegermanBasun, HansIngelsson, MartinLannfelt, LarsKilander, Lena
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