Should CSF Biomarkers Support a Routine Analysis for Early Diagnosis of Alzheimer's Disease?

In view of the availability of drugs that may slow or even halt the progression of Alzheimer's disease (AD), the possibility to routinely discriminate individuals carrying incipient AD is utmost important. The CSF biomarkers beta-amyloid and tau are increasingly used in several countries in Europe for their high diagnostic accuracy in detecting early or even prodromal AD. Up till now, thousands of subjects have been studied either in research or routine setting, giving sensitivity and specificity values invariably above 80%. Despite these clinically relevant results, CSF analysis is still considered only a supportive exam in AD diagnostic work-up. We think there is a great need to improve the medical awareness about the importance to perform lumbar puncture as a routine procedure in the diagnostic assessment of cognitive deterioration. In line with this belief, the first paper of this special issue addresses the usefulness of cerebrospinal fluid analysis for diagnostic definition of cognitive deficits, and the second one further focuses on the ethical issues related to early diagnosis of Alzheimer's disease. As a corollary, the third paper reports some reflections about the actual need in clinical practice of guidelines for diagnosis and management of incipient AD. The fourth paper illustrates what is known about CSF biomarkers for diagnosing AD, and the fifth paper gives a different perspective according to the Canadian guidelines for dementia diagnosis. An up-dated and comprehensive view of crucial issues emerged from large multicentre studies (which have clearly highlighted the inter-centre variability of these determinations) on CSF biomarkers for AD diagnosis is reported in the sixth paper. Accordingly, the seventh paper nicely describes the efforts done for standardization of assay procedures and the eighth paper further goes into details about the many factors inducing variation of amyloid beta concentration, which heavily hampers, at present, a good inter-centre reliability. Besides the state of art about what is known on classical CSF biomarkers for early diagnosis in routine clinical practice, there also are impressive international research initiatives aimed at identifying new biomarkers for neurodegenerative diseases. This issue is thoroughly addressed by the ninth paper, which gives an overview of the EU-funded consortium cNEUPRO. The issue of the role of CSF biomarkers in non-AD dementias is also partly addressed in this special issue. An overview on CSF biomarkers in dementia with Lewy bodies (DLB) is given in the tenth paper, and in the eleventh paper the discriminative power of classical and putative CSF biomarkers for differentiating AD, DLB, and Parkinson's disease with dementia (PDD) is accurately described; finally, the usefulness of classical CSF biomarkers in characterizing CADASIL, a genetic model of subcortical vascular dementia, is also reported. Lucilla Parnetti Jens Wiltfang Kaj Blennow