Spreading of pathology in neurodegenerative diseases: a focus on human studies

By J. Brettschneider, K. Del Tredici, V. Lee, John Q. Trojanowski. Nature Reviews Neuroscience, 2015

748 citations recorded by the source corpus.

The progression of many neurodegenerative diseases is thought to be driven by the template-directed misfolding, seeded aggregation and cell–cell transmission of characteristic disease-related proteins, leading to the sequential dissemination of pathological protein aggregates. Recent evidence strongly suggests that the anatomical connections made by neurons — in addition to the intrinsic characteristics of neurons, such as morphology and gene expression profile — determine whether they are vulnerable to degeneration in these disorders. Notably, this common pathogenic principle opens up opportunities for pursuing novel targets for therapeutic interventions for these neurodegenerative disorders. We review recent evidence that supports the notion of neuron–neuron protein propagation, with a focus on neuropathological and positron emission tomography imaging studies in humans.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/2bbec7af43178355ef91aeb67fc189c85095e213

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Neurology

In Physiology

Citations in the corpus

Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade. (2017, neutral): “3D structure of Alzheimer’s amyloid-β(1-42) fibrils.”
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. (2017, neutral): “…along the pathways of neural connectivity; release of toxic factors (lipid radicals, PUFA oxidation products) possible (Braak and Del Tredici, 2015; Brettschneider et al., 2015) Decreased cortical GPX4 Human brain tissue data indirectly implicate GPX4 impairment (Cardoso et al., 2017) Increased…”
Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria (2016, background): “, different strains of Aß [14,15]; mixed pathology [especially in elderly subjects] [16]; different genetic backgrounds [17–19]; and different relevant risk factors of AD [20]).”
A designer AAV variant permits efficient retrograde access to projection neurons (2016, background): “Error bars represent the SEM. networks, ultimately leading to failure of neurological functions (for a recent review, see Brettschneider et al., 2015).”
Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease (2016, neutral): “…is thought to be pathogenic in a family of diseases termed synucleinopathies, which includes PD, multiple system atrophy, and Lewy body disease (Brettschneider et al., 2015; Luk et al., 2012; Prusiner et al., 2015). aSyn aggregation is a stepwise process, leading to oligomeric species and…”