High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease

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.

Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data

“…Moreover, we found that the influence of Aβ on cognition was not influenced by tau status (i.e., Aβ-tau interaction). These findings are incongruent with previous findings in individuals with MCI as well as in cognitively normal individuals showing that tau and other neurodegenerative features, rather than Aβ, are associated with cognitive impairment and decline in various cognitive domains (Nelson et al, 2012 ; Mormino et al, 2014 ; Pettigrew et al, 2015 ; Brier et al, 2016 ; Degerman Gunnarsson et al, 2016 ; Dumurgier et al, 2017 ; Cerami et al, 2018 ). However, there are noteworthy differences between these previously mentioned studies and our study in determining tau status (CSF vs. PET), cognitive outcome measure used (single test, composite score, or computerized test) and design of the study (cross-sectional cognitive performance vs. longitudinal cognitive decline).…”

Current state of Alzheimer’s fluid biomarkers

“…As with CSF Aβ42, CSF tau has the potential to predict disease progression in cognitively unimpaired individuals [ 301 ] and in those with MCI [ 91 , 285 ]. CSF t-tau has been shown to predict more aggressive disease progression in patients with MCI due to AD or in mild-to-moderate AD [ 65 ].…”

The role of interleukin-33 in patients with mild cognitive impairment and Alzheimer’s disease

“…The main pathophysiology of Alzheimer's disease (AD) involves the accumulation of insoluble forms of amyloid-beta (Aβ) peptide into plaques and the aggregation of the microtubule protein tau into neurofibrillary tangles [1][2][3][4][5]. In addition to the amyloid and tau hypotheses, substantial evidence suggests that innate immune system-mediated actions drive and exacerbate AD pathogenesis [6][7][8][9][10].…”