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


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.
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, SE-751 85, Uppsala, Sweden. malin.degerman.gunnarsson@pubcare.uu.se.
Malin
M
Degerman Gunnarsson
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, SE-751 85, Uppsala, Sweden.
Martin
M
Ingelsson
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska University Hospital, SE-43180, Mölndal, Sweden.
Kaj
K
Blennow
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, SE-751 85, Uppsala, Sweden.
Hans
H
Basun
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, SE-751 85, Uppsala, Sweden.
Lars
L
Lannfelt
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, SE-751 85, Uppsala, Sweden.
Lena
L
Kilander
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000451:nursing*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000451:nursing*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009735:Nursing Homes / Q000706:statistics & numerical data*; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
Alzheimer’s disease; Amyloid-β; CSF; Death in severe dementia; Moderate dementia; NHP; Nursing home placement; Rapid decline; Tau; p-tau