Erschienen:
Springer Science and Business Media LLC, 2016
Erschienen in:Alzheimer's Research & Therapy
Sprache:
Englisch
DOI:
10.1186/s13195-016-0191-0
ISSN:
1758-9193
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-β 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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (<jats:italic>n</jats:italic> = 134) or mild to moderate AD (<jats:italic>n</jats:italic> = 100) who underwent lumbar puncture at a memory clinic and were followed for 2–11 years (median 4.9 years).</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>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.</jats:p>
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