Brain structure and function are determined by four mega-networks: the neuronal, the glial, the immune, and the vascular systems. These four networks are intimately interconnected and affect each other. Brain degenerative diseases affect the dynamics or the stability of a given network, its organization and topology, cell viability, cell numbers, cellular functionality, intra-network cell connectivity, and the interactions with other networks. Impaired dynamics and network instability beyond certain thresholds result in clinical symptoms. A protein that can regulate the dynamics of all the brain mega-networks is the serine/threonine kinase ataxia-telangiectasia mutated ATM, which is missing in ataxia telangiectasia (A-T) patients. The hallmarks of A-T are severe neuromotor dysfunction emanating primarily from progressive cerebellar atrophy, telangiectasia (dilation of blood vessels observed primarily in the eyes), general immunodeficiency, thymic and gonadal dysgenesis, striking predisposition to malignancies (mainly lymphoreticular), and extreme sensitivity to ionizing radiation, and, in some patients, growth retardation, premature aging, and insulin resistance. Here we describe the nature of the brain mega-networks and how they are regulated by ATM.