Epidemiological studies indicate that patients suffering from Alzheimer’s disease have a lower risk of developing lung cancer, and suggest a higher risk of developing glioblastoma. Here we explore the molecular scenarios that might underlie direct and inverse co-morbidities between these diseases. Transcriptomic meta-analyses reveal significant numbers of genes with inverse patterns of expression in Alzheimer’s disease and lung cancer, and with similar patterns of expression in Alzheimer’s disease and glioblastoma. These observations support the existence of molecular substrates that could at least partially account for these direct and inverse co-morbidity relationships. A functional analysis of the sets of deregulated genes points to the immune system, up-regulated in both Alzheimer’s disease and glioblastoma, as a potential link between these two diseases. Mitochondrial metabolism is regulated oppositely in Alzheimer’s disease and lung cancer, indicating that it may be involved in the inverse co-morbidity between these diseases. Finally, oxidative phosphorylation is a good candidate to play a dual role by decreasing or increasing the risk of lung cancer and glioblastoma in Alzheimer’s disease.

This work was funded by the Spanish Ministry of Economics and Competitiveness (grant No’s BIO2012-40205 and BFU2015-71241-R) and it was carried out in the framework of the Platform for Biomolecular and Bioinformatics Resource (PT 13/0001/0030 of the ISCIII), which is funded through the European Regional Development Fund (ERDF). RT-S acknowledges funding from the Generalitat Valenciana (PROMETEOII/2015/021) and the national grant PI14/00894 from the Spanish “Plan Nacional de I + D + I 2013-2016,” co-funded by the “ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).

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