Genes Identified that Play Role in Alzheimer's, Glioblastoma Comorbidity
Patients with Alzheimer's disease are at higher risk of developing glioblastoma and less for lung cancer. A paper published in Scientific Reports by researchers from the National Cancer Research Center (CNIO) and led by Alfonso Valencia, a researcher attached to the CNIO and the Barcelona Supercomputing Center (BSC-CNS), describes the underlying biological processes to these relations of comorbidity.
The increase in life expectancy has caused many people to simultaneously suffer from several diseases. This phenomenon is known as comorbidity and can be a direct relation, when in the presence of a pathology there is more risk of occurrence of another concrete, or inverse, when suffering from a certain condition implies a lower risk of suffering another. Epidemiology has identified several such relationships, such as a lower incidence of cancer in people with certain diseases of the central nervous system.
A study published in the journal PLoS Genetics in 2014 by CNIO researchers showed that genes overexpressed in diseases of the central nervous system (Alzheimer's, Parkinson's and schizophrenia) were under-expressed in cancer (lung, colon and prostate) and vice versa . Understanding the molecular basis of these processes provides important information for the study of the causes of each disease and for the design of possible new therapeutic strategies (drug repositioning).
The work presented now in Scientific Reports delves into the relationship between Alzheimer's disease and brain tumors (glioblastoma in particular), using lung cancer data as a reference and applying a new meta-analytic methodology explicitly developed for this case.
MITOCHONDRIAL ALTERATION AND CHRONIC INFLAMMATION
"The analysis of glioblastoma, which has direct comorbidity with Alzheimer's and also originates from the same organ, has allowed us to better understand the molecular relations of comorbidity between Alzheimer's and cancer and to eliminate tissue-dependent biases , " explains Jon Sánchez-Valle, the first author of the paper.
Analyzes of more than 1000 samples of patients with these diseases have identified 198 genes whose function is significantly altered in all three. Of these, 112 had a similar pattern in Alzheimer's and glioblastoma and the opposite pattern in lung cancer.
By comparing the biological processes altered by the deregulation of these genes, the authors confirm that mitochondrial dysfunction plays a fundamental role in the development of Alzheimer's disease and could also lead to an increased risk of brain tumors in Alzheimer's patients as a consequence Of the establishment of a chronic inflammatory state in the brain. The reduction of energy intake and the generation of reactive oxygen species (ROS) due to altered mitochondrial function would be related to protection against lung cancer in Alzheimer patients.
These results, the authors suggest, could help in the search for new uses for existing drugs and new therapeutic combinations for the treatment of these diseases based on patient-specific genomic information.
A molecular hypothesis to explain direct and inverse co-morbidities between Alzheimer's Disease, Glioblastoma and Lung cancer . Jon Sánchez-Valle, Héctor Tejero, Kristina Ibáñez, José Luis Portero, Martin Krallinger, Fátima Al-Shahrour, Rafael Tabarés-Seisdedos, Anaïs Baudot and Alfonso Valencia ( Scientific Reports 2017). DOI: 10.1038 / s41598-017-04400-6