Current state of Alzheimer’s fluid biomarkers

José Luis Molinuevo, Scott Ayton, Richard Batrla, Martin M. Bednar, Tobias Bittner, Jeffrey Cummings, Anne M. Fagan, Harald Hampel, Michelle M. Mielke, Alvydas Mikulskis, Sid O’bryant, Philip Scheltens, Jeffrey Sevigny, Leslie M. Shaw, Holly D. Soares, Gary Tong, John Q. Trojanowski, Henrik Zetterberg, Kaj Blennow

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/ adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

Original languageEnglish (US)
Pages (from-to)821-853
Number of pages33
JournalActa neuropathologica
StatePublished - Dec 2018


  • Alzheimer’s disease
  • Amyloid
  • Biomarker
  • Blood
  • Cerebrospinal fluid
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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