CSF phospho-tau (p-tau(181)) levels have shown good diagnostic utility in differential diagnosis of Alzheimer disease (AD). Unlike total-tau (t-tau), age related changes of this promising biomarker are sparsely studied. The aim of the study was to determine whether p-tau(181) is dependent on age, cognitive status or gender in patients with different neurological diseases who underwent diagnostic lumbar puncture and who had no clinical evidence of neurodegenerative diseases. CSF levels of p-tau(181) and total-tau (t-tau) of 46 neurologic patients (age range 22-89 years; 22 male, 24 female) were analyzed. Clinical diagnoses were cerebral ischaemia (n = 6), multiple sclerosis (n = 13), epileptic seizures (n = 3), polyneuropathy (n = 9) and other neurological diagnoses (n = 15). Cognitive performance was assessed by the German version of the CERAD battery. The mean level of p-tau(181) was in accordance with previous findings in neurological patients (42.8 +/- 15.3 pg/ml) and did not differ between neurological diseases. In contrast to t-tau (r = 0.38; P = 0.009), p-tau(181) did not correlate significantly to age (r = 0.15; P = 0.308). No influence of cognitive status or gender on p-tau(181) levels could be detected. The study corroborates the independence of p-tau(181) from age, cognitive status, gender and a wide spectrum of neurological diseases. The findings suggest that neither age related neurodegenerative processes nor ischaemic or inflammatory processes are accompanied by tau protein phosphorylation. In contrast, the data support the view that p-tau(181) seems to be a sign of the highly AD-specific pattern of tau phosphorylation during formation of neurofibrillary tangles.