The use of cerebrospinal fluid biomarkers to measure change in neurodegeneration in Alzheimer's disease clinical trials

• Introduction: All recent phase 3 trials of potentially disease-modifying therapies for Alzheimer's disease (AD) have so far failed. Potential reasons include enrolling subjects whose disease is too advanced or who do not have AD pathology, or simply incorrect drug targets. The goal of disease-modifying AD trials is to halt the progress of neuronal damage and death and this can be assessed in vivo using cerebrospinal fluid (CSF) biomarkers.Areas covered: The authors conducted a literature search of the use of CSF biomarkers in disease-modifying AD clinical trials using PubMed. The authors show that CSF biomarkers have only sparsely been used as outcome measures, and where they have, only in small subsets of patients. No clinical trials have yet showed any substantial effects on CSF biomarkers of neurodegeneration.Expert commentary: In future trials, the authors advocate that CSF biomarkers be used more extensively to optimize the chance of detecting positive drug effects. This includes the identification of potential AD patients - already in the early prodromal stage - for inclusion, for stratification, as readout i.e. proximity markers for changes in axonal/neurodegeneration between treatment and placebo groups - this also enables proof of principle verification in the discovery/dose finding phase, and for monitoring of side effects.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Keyword

CSF

biomarkers

clinical trial

Alzheimer's disease

neurodegeneration

creutzfeldt-jakob-disease

csf neurofilament proteins

gamma-secretase

inhibition

mild cognitive impairment

amyloid-beta

total tau

frontotemporal dementia

national institute

double-blind

phospho-tau

Neurosciences & Neurology

Pharmacology & Pharmacy

khann g

1984

neurology

v34

p939

Publication and Content Type

ref (subject category)

art (subject category)