Biomarkers for the diagnosis of Alzheimer’s disease
The characteristic symptoms of Alzheimer’s disease, such as progressive memory loss or other cognitive deficits and behavioral disorders, can make us suspect the diagnosis of this disease. This suspicion can be supported by the determination of biomarkers.
Biomarkers measure the biological changes that occur in the brains of people with the disease and often are useful to confirm or rule out the diagnosis of Alzheimer with high certainty. Some of the most used biomarkers are the measurement of the amyloid protein and the tau protein in cerebrospinal fluid, a liquid that surrounds the central nervous system and that can be obtained through a lumbar puncture. Today we know that biomarkers measured in cerebrospinal fluid are very sensitive and specific for the diagnosis of Alzheimer’s disease and are often useful for monitoring the effect of drugs in clinical trials, but we do not have as much information on how these biomarkers change over time in the same person.
The aim of our study, recently published in the journal Alzheimer’s and Dementia and entitled “Longitudinal cerebrospinal fluid Biomarker trajectories along the Alzheimer’s disease continuum in the BIOMARKAPD study“, was to determine the path of cerebrospinal fluid Alzheimer’s biomarkers over time.
What have we done in this study?
This study was possible thanks to the collaboration of 467 patients and volunteers from 15 centers around the world, (including participants of the SPIN cohort), who received two or more lumbar punctures during their follow-up. In samples of cerebrospinal fluid obtained through these punctures markers that are used for the diagnosis of Alzheimer’s disease were measured, and changes over time on these markers were evaluated.
Neurodegeneration markers associated with tau protein increased 2% per year of baseline age in healthy participants (without cognitive problems). In patients with Alzheimer’s disease, although they have higher levels of these proteins, there is no increase associated with age, but levels stabilize or even decrease.
For the duration of the study (in some people up to 6 years between lumbar punctures), the values of these markers did not change significantly with-in person between the initial puncture and the following ones.
A marker of neuronal damage (NfL) and a marker of neuroinflammation (YKL-40) did show significant changes between the initial puncture and the following ones.
Relevance of the study
Our results are highly relevant for the interpretation of biomarker levels in longitudinal studies. They provide information about the natural evolution of these markers over time, which serves as a starting point to interpret the possible effects of drugs in clinical trials.
The results of this study are the result of the international multi-center project BIOMARKAPD (Biomarkers for Alzheimer’s disease and Parkinson’s disease) that is framed in the European JPND program aimed at research in neurodegenerative diseases.
Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer’s disease continuum in the BIOMARKAPD study. Lleó, A, Alcolea, D, Martínez-Lage, P et al. Alzheimers Dement 2019