CSF and plasma biomarkers for Alzheimer’s disease – use for diagnostics and theragnostics

Kaj Blennow1,*

1University of Gothenburg, Clinical Neurochemistry Lab, Mölndal, Sweden

A panel of CSF biomarkers have been developed for Alzheimer’s disease (AD), including total tau, Aβ42 and phospho-tau, reflecting neuronal degeneration, Aβ deposition and tangle formation. Their role in diagnostics has been evaluated in numerous studies, showing high diagnostic accuracy for AD dementia and also to identify prodromal AD cases in mild cognitive impairment (MCI) cohorts. The performance of CSF Aβ42 has also been compared with amyloid PET, showing excellent agreement.

CSF samples are easily sent from any clinic to the Clinical Neurochemistry Lab performing the analyses, but absolute levels between laboratories, and also between batches of ELISA kits, vary and need to be standardized. 

For this reason, a number of standardization initiatives have been started. The IFCC Work Group for CSF proteins aim is to develop a Certified Reference Material (CRM) and Reference Measurements Procedures (RMP), i.e., a mass spec-based “Golden Standard” method. The aim is to harmonize levels to allow uniform cut-off levels for the CSF biomarkers. New high-quality assays and also assays on fully automated lab analysers are being developed by Biotech companies. Last, assay performance is monitored by the Alzheimer’s Association’s worldwide Quality Control (QC) program. These projects will facilitate the large-scale introduction of CSF biomarkers in clinical diagnostic routine, which will be important to enable early diagnosis of AD the day disease-modifying drugs are approved.

New CSF biomarkers include novel assays to monitor synaptic function and degeneration, such as SNAP-25 and neurogranin. This type of biomarkers may be important to monitor the effect of novel drugs on synaptic function, and might serve as surrogate markers for clinical improvement. 


Last, new technical developments, such as Single Molecule Array (Simoa), show promise to enable measuring the AD biomarkers in blood samples, which may have a position as screening tools at the primary care level.

Keywords: Biomarker development