The current special issue of the Journal of Neural Transmission features 15 papers dealing with the biomarkers of neurodegenerative disorders, and as stated in the title they are neither restricted to one particular disease nor to the given type of diagnostic material. The cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) have evolved over the last three decades from an interesting but peculiar finding without practical meaning, to one of the central diagnostic tools, and this is a very interesting evolution. The first evidence that there is something going on came, at least to my best knowledge, from Delaney, who 30 years ago reported ten AD patients with decreased CSF aluminum concentrations (Delaney 1979). Of course, by far it was not enough to make any clinical use, and the first McKhann criteria (McKhann et al. 1984) spoke no single word about the biomarkers in the CSF. Only with the first papers by Blennow, in the early 1990s, the avalanche started; interestingly enough, however, neither amyloid b (Ab) nor Tau but monoamine metabolites and neuron specific enolase were the first serious biomarker candidates (Blennow et al. 1992, 1994). The consensus report of 1998 defined the criteria a candidate biomarker should fulfill to be accepted for diagnostic purposes (The Working Group on: ‘‘Molecular and Biochemical Markers of Alzheimer’s Disease’’ 1998) and interestingly these criteria, published 15 years ago, remain valid until today. Meanwhile, dozens of expert groups worldwide have struggled to find new biomarkers or to optimize the existing ones. Their efforts are also reflected in the papers published in this issue of the JNT, and they eventually brought about significant change in the approach to the diagnostic utility of the CSF biomarkers: The new McKhann recommendation (McKhann et al. 2011) includes the application of the CSF biomarkers, and moreover, in his comments (McKhann 2011), Dr. McKhann states, ‘‘The most novel aspect of the 3 sets of recommendations is the application of biomarkers, which are measures of a biological fluid or imaging findings that systematically relate to the presence and progression of the underlying disease process’’, continuing with the explanation that the CSF alterations: decreased Ab and increased Tau (along with its phosphorylated form) do reflect pathology of AD: accumulation of amyloid b in plaques and neuronal injury, respectively. Similarly, the research criteria published by Dubois et al. (2007) focussed on the role of the CSF biomarkers, defining them as one of the supportive features for probable AD, and also German diagnostic and treatment guideline recommends CSF biomarkers as a routine diagnostic tool (2009). Finally, a recently published expert consensus describes procedures for the proper collection and preanalytical sample handling (Vanderstichele et al. 2012); moreover, with the growing number of centers performing CSF analyses as a routine diagnostic tool, first international multicenter projects had to start to control and improve inter-laboratory variation of the results (Lewczuk et al. 2006a; Mattsson et al. 2011). Perhaps one issue accented by Dubois et al. is particularly worth a short discussion, as it excellently stresses the value of the CSF biomarkers in AD: cognitively normal people having CSF alterations typical for AD are defined as ‘‘asymptomatic at risk for AD’’. This reflects the most important feature of the CSF biomarkers—their alterations P. Lewczuk (&) Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Department of Psychiatry and Psychotherapy, Universitatsklinikum Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany e-mail: Piotr.Lewczuk@uk-erlangen.de