A Neurochemical Basis for Phenotypic Differentiation in Alzheimer's Disease? Turing's Morphogens Revisited

作者：Whittaker Heather T; Warren Jason D^*

来源：Frontiers in Aging Neuroscience, 2017, 9: 76.

DOI：10.3389/fnagi.2017.00076

• Alzheimer's disease
• dementia
• phenotype
• network
• Turing
• protein

The pathological process underpinning Alzheimer's disease (AD) can manifest as any of several distinctive clinico-anatomical syndromes (Warren et al., 2012). The factors that drive this phenotypic variation remain unclear but are likely to hold important insights into the mechanisms whereby local neurotoxic effects of pathogenic proteins are scaled to distributed brain networks. A theoretical framework for understanding morphological differentiation in biological systems was first outlined in now classic work by Turing (1952), who showed computationally that diffusion of two or more tissue chemicals or "morphogens" reacting across an embryonic cellular network is sufficient to scale initial random fluctuations into stable, often strikingly asymmetric patterns. Here we propose that Turing's theory predicts the phenotypic diversity of AD, as a fundamental consequence of two interacting pathogenic proteins (phosphorylated tau and beta-amyloid) that spread diffusively through a common, distributed neural network.

• 出版日期2017-3-29