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High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease
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.
Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, SE-43180 Molndal, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
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2016 (English)In: Alzheimer's Research & Therapy, ISSN 0065-6755, E-ISSN 1758-9193, Vol. 8, 22Article in journal (Refereed) Published
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Abstract [en]

Background: Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-beta 42 peptide, are biomarkers of Alzheimer's disease (AD) pathology, but few studies have shown an association with AD progression rate. We hypothesized that high CSF tau, as a marker of ongoing neurodegeneration, would predict a more aggressive course of AD, using time to nursing home placement (NHP) as the main outcome. Methods: Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (n = 134) or mild to moderate AD (n = 100) who underwent lumbar puncture at a memory clinic and were followed for 2-11 years (median 4.9 years). Results: Individuals with CSF t-tau in the highest quartile (>= 900 ng/L) had a higher ratio of NHP, both in the total cohort and in patients with MCI only (adjusted HR 2.17 [95 % CI 1.24-3.80]; HR 2.37 [95 % CI 1.10-5.09], respectively), than the lowest quartile. The association between high t-tau levels and future steep deterioration was confirmed in analyses with conversion to moderate dementia (HR 1.66; 95 % CI 1.08-2.56), rapid decline in Mini Mental State Examination score (>= 4-point drop/12 months), and dying in severe dementia as outcomes. Conclusions: To our knowledge, this is the first study to show that high CSF t-tau levels predict early NHP and conversion to moderate dementia in an AD cohort. Selecting patients with high CSF t-tau, indicating more aggressive neurodegeneration and steeper decline, for AD immunotherapy trials might increase the possibility of showing contrast between active treatment and placebo.

Place, publisher, year, edition, pages
2016. Vol. 8, 22
Keyword [en]
Nursing home placement, NHP, Alzheimer's disease, CSF, Tau, p-tau, Amyloid-beta, Rapid decline, Moderate dementia, Death in severe dementia
National Category
Nursing Geriatrics
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URN: urn:nbn:se:uu:diva-298845DOI: 10.1186/s13195-016-0191-0ISI: 000376959600001OAI: oai:DiVA.org:uu-298845DiVA: diva2:948354
Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2017-11-28Bibliographically approved

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Gunnarsson, Malin DegermanIngelsson, MartinBasun, HansLannfelt, LarsKilander, Lena

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