Proteomic studies of cerebrospinal fluid biomarkers of Alzheimer’s disease: an update

ABSTRACT

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease affecting the brain. Today there are three cerebrospinal fluid (CSF) biomarkers, amyloid-β consisting of 42 amino acids (Aβ42), total-tau (t-tau) and phosphorylated-tau (p-tau), which combined have sensitivity and specificity figures around 80%. However, pathological studies have shown that comorbidity is a common feature in AD and that the three currently used CSF biomarkers do not optimally reflect the activity of the disease process. Thus, additional markers are needed.

Areas covered: In the present review, we screened PubMed for articles published the last five years (2012–2017) for proteomic studies in CSF with the criteria that AD had to be included as one of the diagnostic groups. Based on inclusion criteria, 28 papers were included reporting in total 224 biomarker-data that were altered in AD compared to control. Both mass spectrometry and multi-panel immunoassays were considered as proteomic studies.

Expert commentary: A large number of pilot studies have been reported but so far there is a lack of replicated findings and to date no CSF biomarker discovered in proteomic studies has reached the clinic to aid in the diagnostic work-up of patients with cognitive impairment.

KEYWORDS:

• Mass spectrometry
• cerebrospinal fluid
• Alzheimer’s disease
• proteomics
• immunoassays
• biomarker

Declaration of interest

K. Benlow is co-founder of Brain Biomarker Solutions, a GU Ventures-based platform company at the University of Gothenburg and has served at advisory boards for IBL International, Roche Diagnostics and given lectures for Fujirebio Europe.

H. Zetterberg is co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg, Sweden, and has served at advisory boards for Roche Diagnostics, Eli Lilly and Pharmasum Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The study was supported by the Torsten Söderberg Foundation at the Royal Swedish Academy of Sciences, the Knut and Alice Wallenberg Foundation, the European Research Council, the Swedish Research Council, the Swedish Brain Foundation, The Swedish Alzheimer foundation, Gun and Bertil Stohne’s Foundation, Demensförbundet, Gamla Tjänarinnor’s Foundation, Åhlen-stiftelsen, Frimurarestiftelsen, Wallströms och Sjöbloms stiftelse and the Swedish federal government under the ALF agreement.