Current Opinion In Neurobiology | January 13, 2020

Simren J, Ashton NJ, Blennow K and Zetterberg H.

Current Opinion in Nneurobiology. 2019;61:29-39.

doi: https://doi.org/10.1016/j.conb.2019.11.019

Abstract

Highlights•Protein biomarkers in cerebrospinal fluid now define Alzheimer’s disease (AD).•New ultrasensitive techniques have enabled promising replication in blood.•This would enable the use of biomarkers to screen for AD in a primary care setting.•The coexistence of pathologies complicates clinical trials and diagnostics of neurodegenerative diseases (NDDs).•Biomarkers for NDDs that reflect other pathologies are greatly needed.

Over the last twenty years, the characterization of Alzheimer’s disease (AD) patients has progressed from a description of clinical symptomatology followed by neuropathological findings at autopsy to in vivo pathophysiological signatures using cerebrospinal fluid (CSF) and positron emission tomography (PET). Additionally, CSF biomarkers now reflect synaptic pathology, axonal injury and neuroinflammation. Novel techniques are capable of measuring proteins of pathophysiological importance at femtomolar concentrations in blood (e.g. amyloid, tau species and neurofilaments), which enable screening of large populations in the near future. This will be essential for secondary prevention trials and clinical management. However, common diseases such as dementia with Lewy bodies, Parkinson’s disease and frontotemporal dementias, are still without reliable diagnostic biomarkers, although emerging techniques show promising pilot results for some of these diseases. This is likely to change in the next few years, which will be crucial to stratify populations enrolling in clinical trials, since pathologies often coexist.