The Dementia Neurobiology Group and the Genetics in Neurodegenerative Diseases Group of the Sant Pau Biomedical Research Institute (IIB Sant Pau), together with the Memory Unit of the Neurology Service of the Sant Pau Hospital, validate a technique for the early detection of Alzheimer’s disease. The study led by the researchers of San Pablo, which internationally validates the new technique, is entitled “Agreement of Amyloid PET and CSF Biomarkers for Alzheimer’s disease where Lumipulse” and has recently been published in the journal Annals of Clinical and Translational Neurology.
Early detection of Alzheimer’s using biomarkers
The clinical diagnosis of Alzheimer’s disease can sometimes be complicated, either because the symptoms are not very specific or because they are very incipient. In recent years, the scientific community has made a great effort to develop biomarkers of the disease, i.e. biochemical and neuroimaging analysis techniques to facilitate early diagnosis in these cases. The search for biomarkers and the study of their clinical usefulness for the early detection of the disease has been one of the priority lines of research of researchers in Sao Paulo in the last ten years.
How the study has been done
The study involved nearly 100 patients and volunteers from the SPIN study (https://santpaumemoryunit.com/ca/linies-recerca/cohort-spin/) who underwent a lumbar puncture to obtain cerebrospinal fluid. These same participants underwent a brain imaging test (PET) to visualize the presence or absence of cerebral amyloid deposits. In the study, the values of four biomarkers in the fluid analyzed by an automated technique were compared with the amyloid PET images for each participant.
Main results
The comparison between cerebrospinal fluid and amyloid PET allowed us to establish the levels of these four proteins (or “cut-off points”) in the cerebrospinal fluid that best detected the presence or absence of cerebral amyloid deposits. The combination of two proteins, Aß42 and Aß40, allowed to discriminate better the presence/absence of cerebral amyloid than Aß42 in an isolated way. In addition, in this study the Sant Pau researchers have collaborated with the company that develops the reagents to find the normal values of these proteins in healthy people, as was done with cholesterol or glucose in the past. This step is essential to define normal values.
Relevance of the study
Until now, the analysis of Alzheimer’s markers in cerebrospinal fluid was done using manual techniques (ELISA), which implied a great variability between analyses and hindered their implementation in clinical practice. Recently, automated analysis techniques have been developed, much more reproducible and consistent for use as a diagnostic tool. This study allows us to establish optimal cut-off points in our population using an automated technique (Lumipulse). The validation carried out in this study has allowed that since the beginning of the year the analysis of cerebrospinal fluid for the early detection of Alzheimer’s disease has been extended from the field of research to its use in routine care at the Hospital de Sant Pau. It is the first hospital to implement this automated technique in its healthcare routine. These analyses make it possible to confirm or rule out the diagnosis of Alzheimer’s disease in patients with very mild or non-specific symptoms of the disease.
Considerations
Although analyses using automated techniques are much more consistent, there are still certain limitations that cause determinations to vary between different centers. Therefore, the application of the cut-off points detailed in this study should be done cautiously in other centers where the conditions of extraction, processing, and storage of samples differ from those applied in our study.
Reference article:
https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.50873
