Abstract
BackgroundIncreased 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.MethodsOur 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).ResultsIndividuals 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.ConclusionsTo 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0191-0) contains supplementary material, which is available to authorized users.
Highlights
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
During follow-up, 149 patients converted to moderate dementia and 112 patients were admitted to nursing home placement (NHP); all had converted to moderate dementia before this event
This study provides evidence of a biomarker that already at the stage of mild cognitive impairment (MCI) due to AD is a marker of future deterioration rate
Summary
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. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia It is characterized by a gradual cognitive deterioration, loss of function in activities of daily living (ADL), poor quality of life, and shorter survival [1]. It is believed to mediate the formation of abnormally phosphorylated tau in neurofibrillary tangles [5] These two processes are reflected by decreased amyloid-β 42 peptide (Aβ42) and increased phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) [6], while high CSF total tau (t-tau) is a marker
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
