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.

Comparison of cross‐sectional areas and distal‐proximal nerve ratios in amyotrophic lateral sclerosis

“…Across patients with ALS, a similar pattern of proximal nerve atrophy was not observed for ulnar or tibial nerves. This finding may suggest an increased susceptibility of disease involvement for the median nerve in neurodegenerative conditions such as ALS . In support of this hypothesis, from a neurophysiological perspective, previous studies have demonstrated that the median nerve axons have higher excitability than the ulnar axons in patients with ALS .…”

BrainMap VBM: An environment for structural meta‐analysis

“…In an ICA of T1-weighted images of schizophrenia patients and controls combined, Xu et al (2009) The transneuronal spread mechanism begins in an epicenter, often a hub (i.e., the hippocampus, insula, etc. ), where alterations spread along axonal pathways in a "prion-like" manner (Ahmed et al, 2016;Zhou, Gennatas, Kramer, Miller, & Seeley, 2012). (b) The nodal stress mechanism suggests that brain hubs are selectively susceptible to damage from oxidative stress and endothelial damage leading to impairments, such as a leaky blood brain barrier (Crossley et al, 2014).…”

Apraxia screening predicts Alzheimer pathology in frontotemporal dementia

“…As such, AD pathology is preferentially distributed along network connections that are part of the cortical-subcortical, large-scale ‘default mode network’ (DMN), which is intrinsic to healthy brain function 35–37. The DMN is anatomically widely distributed 34. Depending on the actual site of DMN network disintegration, characteristic clinical features associated with distinct forms of AD may arise 37.…”