AUTHOR=Oh Myongin , Weaver Donald F. TITLE=Alzheimer’s disease as a fundamental disease of information processing systems: An information theory perspective JOURNAL=Frontiers in Neuroscience VOLUME=17 YEAR=2023 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1106623 DOI=10.3389/fnins.2023.1106623 ISSN=1662-453X ABSTRACT=

The human brain is a dynamic multiplex of information, both neural (neurotransmitter-to-neuron, involving 1.5×1015 action potentials per minute) and immunological (cytokine-to-microglia, providing continuous immune surveillance via 1.5×1010 immunocompetent cells). This conceptualization highlights the opportunity of exploiting “information” not only in the mechanistic understanding of brain pathology, but also as a potential therapeutic modality. Arising from its parallel yet interconnected proteopathic-immunopathic pathogeneses, Alzheimer’s disease (AD) enables an exploration of the mechanistic and therapeutic contributions of information as a physical process central to brain disease progression. This review first considers the definition of information and its relevance to neurobiology and thermodynamics. Then we focus on the roles of information in AD using its two classical hallmarks. We assess the pathological contributions of β-amyloid peptides to synaptic dysfunction and reconsider this as a source of noise that disrupts information transfer between presynaptic and postsynaptic neurons. Also, we treat the triggers that activate cytokine-microglial brain processes as information-rich three-dimensional patterns, including pathogen-associated molecular patterns and damage-associated molecular patterns. There are structural and functional similarities between neural and immunological information with both fundamentally contributing to brain anatomy and pathology in health and disease. Finally, the role of information as a therapeutic for AD is introduced, particularly cognitive reserve as a prophylactic protective factor and cognitive therapy as a therapeutic contributor to the comprehensive management of ongoing dementia.