| 1. |
- Fourier, Anthony, et al.
(author)
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Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability.
- 2015
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In: Clinica chimica acta; international journal of clinical chemistry. - : Elsevier BV. - 1873-3492. ; 449, s. 9-15
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Journal article (peer-reviewed)abstract
- A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and β-amyloid peptides (Aβ42 and Aβ40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations.
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| 2. |
- Höglund, Kina, 1976, et al.
(author)
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Alzheimer's disease - Recent biomarker developments in relation to updated diagnostic criteria.
- 2015
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In: Clinica chimica acta; international journal of clinical chemistry. - : Elsevier BV. - 1873-3492. ; 449, s. 3-8
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is the most common cause of dementia and is characterized by neuroaxonal and synaptic degeneration accompanied by intraneuronal neurofibrillary tangles and accumulation of extracellular plaques in specific brain regions. These features are reflected in the AD cerebrospinal fluid (CSF) by increased concentrations of total tau (t-tau) and phosphorylated tau (p-tau), together with decreased concentrations of β-amyloid (Aβ42), respectively. In combination, Aβ42, p-tau and t-tau are 85-95% sensitive and specific for AD in both prodromal and dementia stages of the disease and they are now included in the diagnostic research criteria for AD. However, to fully implement these biomarkers into clinical practice, harmonization of data is needed. This work is ongoing through the standardization of analytical procedures between clinical laboratories and the production of reference materials for CSF Aβ42, p-tau and t-tau. To monitor other aspects of AD neuropathology, e.g., synaptic dysfunction and/or to develop markers of progression, identifying novel candidate biomarkers is of great importance. Based on knowledge from the established biomarkers, exemplified by Aβ and its many variants, and emerging data on neurogranin fragments as biomarker candidate(s), a thorough protein characterization in order to fully understand the diagnostic value of a protein is a suggested approach for successful biomarker discovery.
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