CSF biomarkers for Alzheimer’s disease: use in early diagnosis and evaluation of drug treatment

Abstract

Early diagnosis of Alzheimer’s disease is important in initiating symptomatic treatment with acetylcholine esterase inhibitors, and will be of even greater significance if drugs with a potential to slow down the degenerative process, such as β-secretase inhibitors and β-amyloid vaccination, prove to have a clinical effect. During the last decade, research efforts have focused on developing cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease. In this review, the background and principles for, and the diagnostic performance of, the CSF biomarkers total tau, phosphorylated tau and the 42-amino acid form of β-amyloid, are reviewed. New candidate CSF biomarkers and new strategies, including multiparameter immunoassays and CSF proteomics techniques, in the search of additional CSF biomarkers are also reviewed. Finally, the rationale for the use of CSF biomarkers to identify and monitor the biochemical effect of new drug candidates is reviewed.

Keywords::

• Alzheimer’s disease
• β-amyloid
• biomarker
• cerebrospinal fluid
• diagnosis
• mass spectrometry
• mild cognitive impairment
• multiparameter assay
• phosphorylated tau
• proteomics
• total tau