Article

NeuroRX

, Volume 1, Issue 2, pp 213-225

First online:

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

  • Kaj BlennowAffiliated withDepartment of Clinical Neuroscience, Section of Experimental Neuroscience, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital Email author 

Summary

The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer’s disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of β-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson’s disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as γ-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

Key Words

Alzheimer’s disease cerebrospinal fluid biomarker tau phosphorylated tau β-amyloid