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Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease

  • Henrik ZetterbergEmail author
  • Jonathan M. Schott
Protocol
Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, which typically shows an initial predilection for brain regions involved in episodic memory consolidation before progressing to affect also other cognitive functions. Neuropathologically, the disease is characterised by accumulation of a 42-amino acid-long protein called amyloid β (Aβ42), as well as N-terminally truncated fragments thereof in extracellular senile plaques. In addition to senile plaques, there are intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuroaxonal degeneration and loss. Clinical chemistry tests for these pathologies have been developed and applied to cerebrospinal fluid samples. Here, we review what these markers have taught us about the disease process in AD and how they can be used as diagnostic tests in clinical practice as well as inclusion criteria and outcome measures for clinical trials. We describe both how such analyses are currently performed in clinical chemistry laboratories and the ongoing efforts to standardise analysis between different sites. Finally, we are also providing an overview of new markers in various stages of development and implementation.

Key words

Alzheimer’s disease Biomarkers Cerebrospinal fluid Plasma Tau Amyloid Clinical trials Clinical diagnosis 

Abbreviations

AD

Alzheimer’s disease

fAD

Familial AD

CJD

Creutzfeldt-Jakob disease

APP

Amyloid precursor protein

sAPPα

Soluble APP alpha

sAPPβ

Soluble APP beta

BACE1

Beta-site APP-cleaving enzyme

CNS

Central nervous system

CSF

Cerebrospinal fluid

T-tau

Total-tau

P-tau

Phospho-tau

Aβ42

Amyloid β-42

MCI

Mild cognitive impairment

NFL

Neurofilament light

TGF-β

Transforming growth factor-β

TNF-α

Tumour necrosis factor α

IL-1β

Interleukin 1β

CCL2

C-C chemokine ligand 2

CV

Coefficient of variation

HIV

Human immunodeficiency virus

QC

Quality control

GCBS

Global Consortium for Biomarker Standardization

IFCC

International Federation of Clinical Chemistry and Laboratory Medicine

ELISA

Enzyme-linked immunosorbent assay

Notes

Acknowledgements

We gratefully acknowledge the support of the Leonard Wolfson Experimental Neurology Centre. Work in the authors’ laboratories is supported by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Alzheimer’s Association, Swedish State Support for Clinical Research, Alzheimer’s Research UK and the NIHR Queen Square BRU in dementia. We wish to thank colleagues, patients and their families for generating the extensive literature that was reviewed here.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and NeurochemistryThe Sahlgrenska Academy at the University of GothenburgGöteborgSweden
  2. 2.Department of Molecular NeuroscienceUCL Institute of NeurologyQueen Square, LondonUK
  3. 3.Dementia Research CentreUCL Institute of NeurologyQueen Square, LondonUK

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