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

• Published in: Frontiers in aging neuroscience Vol. 9; p. 76
• Main Authors: Whittaker, Heather T, Warren, Jason D
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 29.03.2017; Frontiers Media S.A
• Subjects: Aging; Alzheimer's disease; Cerebral hemispheres; Cortex (cingulate); Cortex (frontal); Cortex (parietal); Morphogenesis; Neural networks; Neurodegenerative diseases; Neuroscience; Occipital lobe; Pathogenesis; Pigmentation; Predator-prey interactions; Prefrontal cortex; Prey; Proteins; Star & galaxy formation; Tau protein; Temporal cortex; Temporal lobe; Theory; University colleges; β-Amyloid; United Kingdom > UK; phenotype; dementia; Turing; Alzheimer's disease; protein; network
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2017.00076

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. Turing showed that it is relatively straightforward mathematically to extend the reaction–diffusion framework of “homogeneity breakdown” from a ring to a sphere (or shell) of cells. Since Turing's original formulation, his theory has been shown to hold for an extraordinary variety of applications, ranging from coat pigmentation patterns in animals to predator-prey relationships in ecosystems, crime hotspots in communities, sand ripples, and galaxy formation (Murray, 1990; Ball, 2015). Each panel shows a schematic axial projection of the cerebral hemispheres and the top left panel indicates key anatomical regions, including components of the “default-mode network” (in bold italics): aTL, anterior temporal lobe; FP, frontal pole; hip, hippocampus; iFC, inferior frontal cortex; mPFC, medial prefrontal cortex; TPJ, temporo-parietal junction; OC, occipital cortex; pCC, posterior cingulate cortex. In particular, Turing activation patterns emerge where the firing rates of connected neurons are governed by disproportionate excitatory vs. inhibitory inputs acting over different spatial ranges. Besides physical diffusion between neurons (Warren et al., 2013), tau and beta-amyloid have complex effects on synaptic and neurotransmitter physiology that might establish such Turing field effects.