The Sant Pau Memory Unit has published a study that establishes reference values for a technique that allows the early detection of Alzheimer’s disease. This technique detects alterations in disease-related proteins in the cerebrospinal fluid of patients by means of an automated analysis.
The study entitled “Agreement of Amyloid PET and CSF Biomarkers for Alzheimer’s disease on Lumipulse” has been published in Annals of Clinical and Translational Neurology.
Early detection of Alzheimer’s by biomarkers
Sometimes, the clinical diagnosis of Alzheimer’s disease can be difficult, either because symptoms are not specific or because they are very mild. In recent years, the scientific community has made a great effort to develop biomarkers of the disease, that is, techniques of biochemical analysis and neuroimaging that facilitate early diagnosis in these cases. The search for biomarkers and the study of their clinical utility for the early detection of the disease has been one of the priority research lines in the Sant Pau Memory Unit in the last ten years.
What have we done in this study?
The study had the participation of nearly 100 patients and volunteers from the SPIN study who underwent a lumbar puncture for the obtaining of cerebrospinal fluid. These participants took a cerebral image test (PET) to visualize the presence or absence of brain amyloid deposits. The study compared the values of four biomarkers in the liquid analyzed by means of an automated technique with amyloid PET images for each participant.
The comparison between cerebrospinal fluid and amyloid PET allowed us to establish the levels of these four proteins (or “cut-offs”) in the cerebrospinal fluid that best detected the presence or absence of brain amyloid deposits. We observed that the combination of two proteins, Aß42 and Aß40, allowed a better discrimination of the presence / absence of cerebral amyloid compared to Aβ42 alone. In addition, in this study the Sant Pau Memory Unit has collaborated with the company that develops these reagents to find the normal values of these proteins in healthy people, as was the case with cholesterol or glucose in the past. This step is essential to define the values of normality.
Relevance of the study
So far, the analysis of Alzheimer’s markers in cerebrospinal fluid was done using manual techniques (ELISA), which imply a great variability between the analysis making it difficult to implement in clinical practice. Recently, automated analysis techniques have been developed, much more reproducible and consistent for their use as a diagnostic tool. The present study establishes optimal cut-off points in our population using an automated technique (Lumipulse).
Thanks to the validation carried out in this study, since the beginning of the year the analysis of cerebrospinal fluid for the early detection of Alzheimer’s disease has extended from the field of research to its use in clinical routine at the Sant Pau hospital. It is the first hospital in Spain that implements this automated technique in its routine care. These analyses can usually confirm or rule out the diagnosis of Alzheimer’s disease in patients with very slight or very specific symptoms of the disease.
Although analyses using automated techniques are much more consistent, there are still certain limitations that can cause variations in the determinations across different centers. For this reason, cut-off points detailed in this study must be applied cautiously in other centers where the conditions for extraction, processing and storage of the samples differ from those applied in our study.