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Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype
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.
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2009 (English)In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 27, no 5, 458-464 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/AIMS: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. METHODS: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. RESULTS: The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. CONCLUSIONS: CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.

Place, publisher, year, edition, pages
Karger , 2009. Vol. 27, no 5, 458-464 p.
Keyword [en]
Alzheimer’s disease, Mild cognitive impairment, Biomarkers, Cerebrospinal fluid, Tau, Phospho-tau, Amyloid-β, Apolipoprotein E, Disease progression
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-123101DOI: 10.1159/000216841ISI: 000266098300008PubMedID: 19420940OAI: oai:DiVA.org:uu-123101DiVA: diva2:312285
Available from: 2010-04-23 Created: 2010-04-23 Last updated: 2010-07-28Bibliographically approved

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Blom, Elin S.Giedraitis, VilmantasLannfelt, LarsIngelsson, Martin

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