The diagnosis of Alzheimer’s disease and frontotemporal dementia or FTD can be hard. The use of biomarkers such as the levels of different proteins in the cerebrospinal fluid allows to improve the accuracy of the diagnosis. Specifically, protein levels related to the processing of amyloid precursor protein (APP) have been linked to cerebral amyloid protein deposition, which is a fundamental step in the development of Alzheimer’s disease. However, these proteins have also been found altered in the cerebrospinal fluid in diseases in which there is no cerebral deposit of amyloid protein, such as frontotemporal dementia.
Our recent study, entitled “APP ‐ derived peptides reflect neurodegeneration in frontotemporal dementia” has been published in Annals of Clinical and Translational Neurology.
What have we done in this study?
In this study, we compared the levels of proteins related to the processing of the amyloid precursor protein in patients with frontotemporal dementia, Alzheimer’s disease and in healthy volunteers. To do this, we included more than 200 participants recruited at the Hospital de Sant Pau (SPIN cohort) and at the Hospital Clínic de Barcelona. Specifically, we studied the relationship between the levels of these proteins in the cerebrospinal fluid with magnetic resonance data and regional gene expression data from the Allen Brain Atlas project.
The main finding of this work was that patients with frontotemporal dementia showed a specific protein profile related to APP processing, which is different from that observed in patients with Alzheimer’s disease. In addition, in patients with frontotemporal dementia, protein levels related to APP processing were related to brain changes observed in magnetic resonance imaging and cognitive measures, suggesting that it could be a good marker to study the course of disease.
Relevance of the study
This study has important implications for the clinical diagnosis of patients with frontotemporal dementia and patients with Alzheimer’s disease. Specifically, the results support the use of the Aß1-42/Aß1-40 ratio over Aß1-42 alone for the differentiation of patients with frontotemporal dementia from patients with Alzheimer’s disease. In summary, the results of this work contribute to improving the early diagnosis of patients with frontotemporal dementia and Alzheimer’s. This is a fundamental step in the design of clinical trials that allow testing the efficacy of new treatments for these terrible diseases.