An international research team, led by the University of Lisbon (UL) and the University of Coimbra (UC), conducted a study to better understand the biochemical profiles of patients diagnosed with mild cognitive impairment with Alzheimer's markers (MCI-AD). In this context, the scientists were able to identify two distinct subgroups of the disease, a discovery that they believe could contribute to improving clinical trials, which are fundamental to the knowledge and treatment of this pathology that still has no cure.
With the increase in average life expectancy, the number of people affected by Alzheimer's disease has been rising all over the world, and it is the most common cause of dementia. As it is a disease with no known cause (it is only known that there are various risk factors), the medical and scientific communities have dedicated themselves to finding answers as to its origin and to identifying new and better treatments, particularly through clinical trials that help to understand the manifestation of the disease, its progression and impacts.
However, "there have been no comprehensive solutions from clinical trials in the last decade, which could possibly be due to the fact that we are dealing with a patient population that is considered homogeneous, when biochemically they are heterogeneous, as proven in our study," explains Bruno Manadas, a researcher at the UC Center for Neuroscience and Cell Biology (CNC-UC) and the Center for Innovation in Biomedicine and Biotechnology (CiBB) and one of the authors of the study.
In this scientific article - entitled Pathophysiological subtypes of mild cognitive impairment due to Alzheimer's disease identified by CSF proteomics and published in the journal Translational Neurodegeneration - the researchers were able to show "the presence of biochemical subgroups within a well-defined clinical group of individuals with mild cognitive impairment with Alzheimer's biomarkers, which may point to the existence of different mechanisms of origin and progression of the disease", says Bruno Manadas.
The research also made it possible to "demonstrate that there are more proteins - in addition to beta-amyloid and tau - that make it possible to distinguish between patients with DCL-DA and patients with mild cognitive impairment (DCL) without markers of Alzheimer's disease," adds the researcher. The team believes that these findings could lead to clinical trials with higher efficacy rates in the future, as they provide new information on the different biochemical profiles of the disease.
This study involved national (68) and international (194) patients, with a total of 262 participants. Firstly, there was a clinical evaluation, in which all participants were assessed to identify whether or not they had mild cognitive impairment (a condition associated with the loss of cognitive abilities to a greater extent than would be expected given the patient's age). Then, in the DCL patients, cerebrospinal fluid (CSF, the fluid that circulates around brain structures) was collected and subsequently molecularly characterized. This approach made it possible to identify which of these patients (with DCL) had markers for Alzheimer's disease.
Subsequently, using data analysis tools and machine learning - in collaboration with researchers from the Faculty of Sciences of the University of Lisbon (FCUL) - the protein profiles of cerebrospinal fluids were analyzed. This analysis revealed that the patients could be classified into two subgroups: the immune dysfunction and blood-brain barrier impairment group; and the hyperplasticity-related protein alterations group.
This means that there are at least two profiles of early-stage Alzheimer's patients that can be considered in clinical trials. Currently, "Alzheimer's patients recruited for these trials are assessed as a single group, thus not considering their different biochemical profiles," the UC researcher points out. "This differentiation could lead to clinical trials with higher efficacy rates and, as such, it is important for the clinical and pharmaceutical community to be aware of these subgroups that we have identified," he highlights.
The study was carried out as part of the research project Beyond Beta-Amyloid - Early Pathogenic Changes in Alzheimer's Disease, funded by the Foundation for Science and Technology, which is led by Alexandre de Mendonça, a professor at the Faculty of Medicine of the University of Lisbon (FMUL), and co-coordinated by Bruno Manadas.
New stages of research will now follow, since "the continuity of this study will be essential to understand whether we are facing a new classification of Alzheimer's patients in their early stages," says Bruno Manadas.
Other researchers also took part in the study: Daniela Moutinho (FMUL), Vera Mendes (CNC-UC and CiBB), Alessandro Caula (FCUL and University of Bologna), Sara Madeira (FCUL), Inês Baldeiras (CNC-UC, CiBB and UC Faculty of Medicine), Manuela Guerreiro (FMUL), Sandra Cardoso (FMUL), Johan Gobom (University of Gothenburg and Sahlgrenska University Hospital), Henrik Zetterberg (Hong Kong Center for Neurodegenerative Diseases, University of Wisconsin-Madison, UK Dementia Research Institute, University of Gothenburg, Sahlgrenska University Hospital and University College London), Isabel Santana (Neurology Service of the Coimbra Local Health Unit, CNC-UC, CiBB and UC Faculty of Medicine) and Helena Aidos (FCUL).
The scientific article is available here.
Catarina Ribeiro w/ CNC-UC
