Copyright Ó Blackwell Munksgaard 2005
Acta Neurol Scand 2005: 111: 114–117 DOI: 10.1111/j.1600-0404.2005.00370.x
ACTA NEUROLOGICA SCANDINAVICA
Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis Jime´nez-Jime´nez FJ, Herna´nz A, Medina-Acebro´n S, de Bustos F, Zurdo JM, Alonso H, Puertas I, Barcenilla B, Sayed Y, CabreraValdivia F. Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neurol Scand 2005: 111: 114–117. Ó Blackwell Munksgaard 2005. Objective – To elucidate whether cerebrospinal fluid (CSF) concentrations of the microtubule-associated tau protein are related to the risk for sporadic amyotrophic lateral sclerosis (SALS). Patients/ Methods – We measured tau concentrations in the CSF of 18 patients with SALS and 75 age- and sex-matched controls, using a specific ELISA method. Results – The mean CSF concentrations of tau protein did not differ significantly between SALS patient and control groups, were not influenced by the clinical form (spinal vs bulbar) of ALS, and were not correlated with age, age at onset, and duration of the disease. Conclusions – CSF tau concentrations are not a biochemical marker of ALS.
F. J. Jimnez-Jimnez1, A. Hernnz2, S. Medina-Acebrn2, F. de Bustos3, J. M. Zurdo1, H. Alonso1, I. Puertas1, B. Barcenilla1, Y. Sayed1, F. Cabrera-Valdivia1 1 Department of Neurology Hospital Universitario ÔPrncipe de Asturias’, Universidad de Alcal, Alcal de Henares-Madrid, Madrid, Spain; 2Department of Biochemistry, Ciudad Sanitaria La Paz, Spain; 3 Department of Biochemistry, Hospital Nuestra SeÇora del Prado, Talavera de la Reina, Toledo, Spain
Key words: amyotrophic lateral sclerosis; motoneuron disease; tau protein; cerebrospinal fluid Flix Javier Jimnez-Jimnez, C/Marroquina 14, 3°B, E-28030, Madrid, Spain Tel.: 34-63-6968395 Fax: 34-91-3280704 e-mail:
[email protected] Accepted for publication September 27, 2004
The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) is unknown. It has been suggested a role of genetic and environmental factors, autoimmune mechanisms, oxidative stress, excitotoxicity, viral infection, cytoskeletal abnormalities, and loss of trophic support (1, 2). Tau protein is a phosphorylated microtubuleassociated protein that is considered as important for maintaining the stability of axonal microtubules involved in the mediation of fast axonal transport of synaptic constituents. Following neuronal damage, tau is released into extracellular space and may be increased in the cerebrospinal fluid (CSF) (3). CSF tau concentrations have been found increased in CNS parenchymal diseases, including neurodegenerative disorders, encephalitis, ischemic stroke, intracerebral hemorrhage (4), and multiple sclerosis (4, 5). Kapaki et al. (5) reported normal CSF tau concentrations in 17 patients with sporadic ALS (SALS) compared with 29 controls. A similar finding was reported by Sjo¨gren et al. (6) in 114
11 patients with ALS compared with 17 matched controls, although these authors found decreased levels of CSF beta-amyloid-42 in patients with ALS. On the contrary, Sussmuth et al. (7) reported increased CSF tau concentrations in 70% of their 20 SALS patients compared with 20 matched controls. In this study we assessed the lumbar CSF concentrations of total tau protein in a series of patients with ALS and in age- and sex-matched controls, trying to elucidate whether high CSF tau levels could be a biochemical marker for SALS, which could reflect neuronal damage. Patients and methods
We studied 18 patients with defined SALS, according to the criteria developed by the World Federation of Neurology Subcommittee on Motor Neuron Disease at El Escorial (8), and 75 ageand sex-matched controls. Unselected SALS patients were recruited from outpatients making
CSF tau and amyotrophic lateral sclerosis the first visit to the Department of Neurology of the Hospital Universitario ÔPrincipe de AsturiasÕ. None of them have cognitive impairment. Informed consent was obtained in each case. The control group comprised 75 ÔhealthyÕ patients, who underwent lumbar puncture because of suspected (but not confirmed) subarachnoid hemorrhage or pseudotumor cerebri, oculomotor palsies or other indications in the usual neurological survey. Routine CSF analysis was normal in each patient or control included in the study. Informed consent was obtained in each case. The clinical features of both study groups are summarized in Table 1. The following exclusion criteria were applied both to patients and controls: (a) ethanol intake higher than 80 g/day in the last 6 months; (b) previous history of chronic hepatopathy, chronic renal failure, hematological or autoimmune disease; (c) previous history of severe systemic disease. Lumbar CSF samples were taken from each fasted patient or control between 8.00 and 10.00 a.m. Traumatic spinal punctures were excluded from the study. The CSF specimens were collected in polyethylene tubes, frozen at )30°C and protected from light exposure with aluminum foil until analysis. The storage time was similar for SALS patient and control groups. The determinations were performed blindly. The samples were collected during a 2-year period. Glucose and total protein concentrations in CSF were determined with standard methods using a Hitachi 704 autoanalyser (Boehringer-Mannheim, Mannheim, Germany). These values were normal in the patients included in the study. Tau protein was measured in CSF with a commercial tauspecific sandwich ELISA (Innogenetics, Ghent, Belgium). The sensitivity was measured
