Omics technologies offer great promises for improving our understanding of diseases. The integration and interpretation of such data pose major challenges, calling for adequate knowledge models. Disease maps provide curated knowledge about disorders' pathophysiology at the molecular level adapted to omics measurements. However, the expressiveness of disease maps could be increased to help avoiding ambiguities and misinterpretations and to reinforce their interoperability with other knowledge resources. Ontologies are an adequate framework to overcome this limitation, through their axiomatic definitions and logical reasoning properties. We introduce the Disease Map Ontology (DMO), an ontological upper model based on systems biology terms. We then propose to apply DMO to Alzheimer's disease (AD). Specifically, we use it to drive the conversion of AlzPathway, a disease map devoted to Alzheimer's disease, into a formal ontology: AD Map Ontology (ADMO). We demonstrate that it allows one to deal with issues related to redundancy, naming, consistency, process classification and pathway relationships. Furthermore, we show that it can store and manage multi-omics data. Finally, we expand the model using elements from other resources, such as clinical features contained in the ADO (AD Ontology), resulting in an enriched model called ADMO-plus. The current versions of DMO, ADMO and ADMOplus are freely available at http://bioportal.bioontology.org/ontologies/ADMO.