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Biomarkers for Alzheimer disease - current status and prospects for the future.

Artikel i vetenskaplig tidskrift
Författare Kaj Blennow
Henrik Zetterberg
Publicerad i Journal of internal medicine
Volym 284
Nummer/häfte 6
Sidor 643-663
ISSN 1365-2796
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 643-663
Språk en
Länkar dx.doi.org/10.1111/joim.12816
Ämneskategorier Neurokemi


Accumulating data from clinical research support that the core Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau) reflect key elements of AD pathophysiology. Importantly, a large number of clinical studies very consistently show that these biomarkers contribute with diagnostically relevant information, also in the early disease stages. Recent technical developments have made it possible to measure these biomarkers using fully automated assays with high precision and stability. Standardization efforts have given Certified Reference Materials for CSF Aβ42, with the aim to harmonize results between assay formats that would allow for uniform global reference limits and cut-off values. These encouraging developments have led to that the core AD CSF biomarkers have a central position in the novel diagnostic criteria for the disease and in the recent National Institute on Aging and Alzheimer's Association biological definition of AD. Taken together, this progress will likely serve as the basis for a more general introduction of these diagnostic tests in clinical routine practice. However, the heterogeneity of pathology in late-onset AD calls for an expansion of the AD CSF biomarker toolbox with additional biomarkers reflecting additional aspects of AD pathophysiology. One promising candidate is the synaptic protein neurogranin that seems specific for AD and predicts future rate of cognitive deterioration. Further, recent studies brings hope for easily accessible and cost effective screening tools in the early diagnostic evaluation of patients with cognitive problems (and suspected AD) in primary care. In this respect, technical developments with ultrasensitive immunoassays and novel mass spectrometry techniques give promise of biomarkers to monitor brain amyloidosis (the Aβ42/40, or APP669-711/Aβ42 ratios), and neurodegeneration (tau and neurofilament light proteins) in plasma samples, but future studies are warranted to validate these promising results further. This article is protected by copyright. All rights reserved.

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