A bird’s eye view to the homeostatic, Alzheimer and Glioblastoma attractors

Abstract

A well known paradigm in molecular genetics expresses that local maxima of fitness in gene expression space are related to biological viable states [1]. This picture has been applied to the description of cell fates along differentiation lines [2]. However, to the best of our knowledge, there are no plots based on real data for a given tissue representing at least a partial landscape with more than two of these maxima. We provide a drawing for white matter of the brain in which the normal state is represented along with the glioblastoma (GBM) attractor and the seemingly modest maximum related to Alzheimer disease (AD). The plot shows that GBM and AD are opposite alternatives, as epidemiological [3,4,5,6] and molecular biology studies [7,8,9] suggest, and indicates a path or corridor for normal aging, in accordance with the programmatic aging theory [10,11]. At the gene level, there are genes varying in the same way in the aging, AD progression and cancer processes, whereas there are also genes indicating the disjunctive between AD and GBM. An example of the latter is the MMP9 protein-coding gene, playing an important role in tumor invasion [12,13], but known also as a neuroprotector, controlling the interactions between axons and beta-amyloid fibers [14]. Deviations of the gene expression value from its reference in normal tissue may indicate either a potential progression to AD (under-expression) or to GBM (over-expression). This unusual view, following from a simple plot, may help understand the relations between AD and GBM biology and identify useful gene markers for both processes. We anticipate that similar diagrams could be important in other tissues.