Neuronal network disintegration: common pathways linking neurodegenerative diseases

Abstract

Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration.

Keywords: ALZHEIMER'S DISEASE; COGNITION; DEMENTIA; MOTOR NEURON DISEASE; NEUROANATOMY.

Figure 1

Clinical and pathological overlap in neurodegeneration: showing overlap at both a phenotypic and pathological level between multiple neurodegenerative conditions.

Figure 2

Neurodegenerative network map: proposed way forward for a collaborative approach based on phenotypic variation, imaging, pathology and genetics for investigating the neural networks and their contribution to the pathophysiological bases of neurodegenerative conditions. A better understanding of the neural networks involved is likely to translate into better targeted treatments based on these networks. DTI, diffusion tensor imaging; PET, positron emission tomography.