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Cerebro-spinal fluid biomarker levels: phosphorylated tau (T) and total tau (N) as markers for rate of progression in Alzheimer's disease

Journal article
Authors C. Wattmo
Kaj Blennow
O. Hansson
Published in BMC Neurology
Volume 20
Issue 1
ISSN 1471-2377
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Keywords Alzheimer's disease, Cholinesterase inhibitors, Cognition, Activities of, daily living, Apolipoprotein E, Treatment effect, Disease progression, CSF biomarkers, AT(N), Tau, csf biomarkers, clinical-diagnosis, rating-scale, predict, dementia, protein, decline, hypothesis, inhibitors, stability, Neurosciences & Neurology
Subject categories Psychiatry, Neurochemistry


Background We investigated the potential associations between cerebro-spinal fluid (CSF) levels of phosphorylated tau (P-tau) and total tau (T-tau) with short-term response to cholinesterase inhibitor (ChEI) treatment, longitudinal outcome and progression rates in Alzheimer's disease (AD). Methods This prospective, observational study included 129 participants clinically diagnosed with mild-to-moderate AD, who underwent a lumbar puncture. The CSF biomarkers amyloid-beta(1-42) (A beta(42)), P-tau and T-tau were analysed with xMAP technology. Cognitive, global, instrumental and basic activities of daily living (ADL) capacities at the start of ChEI therapy and semi-annually over 3 years were evaluated. Results All patients had abnormal A beta(42) (A+). Fifty-eight individuals (45%) exhibited normal P-tau and T-tau (A+ T- (N)-), 12 (9%) abnormal P-tau/normal T-tau (A+ T+ (N)-), 17 (13%) normal P-tau/abnormal T-tau (A+ T- (N)+) and 42 (33%) abnormal P-tau and T-tau (A+ T+ (N)+). The participants with A+ T+ (N)+ were younger than A+ T- (N)+ at the estimated onset of AD and the initiation of ChEIs. The proportion of 6-month responders to ChEI and deterioration/year after start of treatment did not differ between the AT(N) profiles in any scales. A higher percentage of globally improved/unchanged patients was exhibited in the A+ T- (N)- group after 12, 30 and 36 months of ChEI therapy but not at other assessments. In apolipoprotein E (APOE) epsilon 4-carriers, linear relationships were found between greater cognitive decline/year and higher tau; Mini-Mental State Examination score - T-tau (r(s) = - 0.257, p = 0.014) and Alzheimer's Disease Assessment Scale-cognitive subscale - P-tau (r(s) = - 0.242, p = 0.022). A correlation between faster progression in instrumental ADL (IADL) and higher T-tau was also detected (r(s) = - 0.232, p = 0.028). These associations were not demonstrated in non-epsilon 4-carriers. Conclusions Younger age and faster global deterioration were observed in AD patients with pathologic tau and neurodegeneration, whereas more rapid cognitive and IADL decline were related to higher P-tau or T-tau in APOE epsilon 4-carriers only. The results might indicate an association between more pronounced tau pathology/neuronal injury and the APOE epsilon 4-allele leading to a worse prognosis. Our findings showed that the AT(N) biomarker profiles have limited utility to predict AD progression rates and, thus, measure change and interpreting outcomes from clinical trials of future therapies.

Page Manager: Webmaster|Last update: 9/11/2012

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