Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry

Abstract

In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-b positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders. ARTICLE HISTORY

The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders

“…In recent years, advances in the field of biomarkers have been instrumental in understanding the neurobiology underlying these disorders. Currently, biomarkers are essential to define the long preclinical stages, to achieve early diagnosis, to improve the selection of participants in clinical trials and to monitor the effect of drugs targeted to specific pathological pathways [1,2]. In the Sant Pau Memory Unit, as in many other teams specialized in neurodegenerative diseases, we have progressively adapted our clinical routine and research programs to incorporate the different biomarkers that are developed in the field.…”

Agreement between 18F-Florbetapir PET imaging and cerebrospinal fluid Aβ1-42, Aβ1-40, tTau and pTau measured on the LUMIPULSE G fully automated platform

“…Biomarkers of different modalities have been investigated in AD, but those that are more widely implemented are cerebrospinal fluid (CSF) biomarkers and imaging techniques. In CSF, a combination of low levels of Aβ1-42 and high levels of total tau (tTau) and 181-phosphorylated tau (pTau) has proven high accuracy to detect AD pathophysiology, even before the appearance of symptoms [5]. Pathological studies have shown that low levels of Aβ1-42 in CSF are associated to high amyloid plaques deposition [6,7], and levels of tTau and pTau in CSF correlate with neuronal loss and neurofibrillary tangle burden [7,8].…”

Exploratory analyses suggest less cognitive decline with nilvadipine treatment in very mild Alzheimer’s disease subjects

“…Longitudinal profiling of CSF Aβ in AD animal models shows that, with AD progression, CSF Aβ42 levels decline first but Aβ40 levels do not fall until the very late stages of AD pathology (45). In addition, recent clinical studies have shown that CSF Aβ42/Aβ40 ratios have a better concordance with amyloid PET imaging for biomarker-based diagnosis of AD than using either Aβ42 or Aβ40 alone (46), and that this ratio is consistently low in AD subjects with high brain amyloid deposition (46,47). In the present study, in mild AD patients, CSF Aβ42/Aβ40 ratios increased in nilvadipine-treated subjects compared to placebo-treated subjects.…”