Parkinsonism and motor neuron disorders: Lessons from Western Pacific ALS/PDC

Spencer, Peter S.

doi:10.1016/j.jns.2021.120021

Cited by 16 publications

(9 citation statements)

References 106 publications

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“…Its incidence in the recent past was 50-100 times that of ALS in the United States [29]. Based on its rapid decline over the past several decades [30,31], the endemic has been attributed to an environmental cause rather than a genetic one [28,32]. Thus, ALS-PDC has long been considered a potential "Rosetta Stone" for understanding the pathogenesis of neurodegenerative disorders.…”

Section: F I G U R Ementioning

confidence: 99%

Misfolded alpha‐synuclein in amyotrophic lateral sclerosis: Implications for diagnosis and treatment

Smith,

Hovren,

Bowser

et al. 2024

Euro J of Neurology

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BackgroundAlpha‐synuclein (α‐Syn) oligomers and fibrils have been shown to augment the aggregation of TAR DNA‐binding Protein 43 (TDP‐43) monomers in vitro, supporting the idea that TDP‐43 proteinopathies such as ALS may be modulated by the presence of toxic forms of α‐Syn 1. Recently, parkinsonian features were reported in a study of European patients 2 and Lewy bodies have been demonstrated pathologically in a similar series of patients 3. Based on these and other considerations, we sought to determine whether seed‐competent α‐Syn can be identified in spinal fluid of patients with ALS including familial, sporadic, and Guamanian forms of the disease.MethodsBased on the finding that α‐Syn has been found to be a prion‐like protein, we have utilized a validated α‐Synuclein seed amplification assay to determine if seed‐competent α‐Syn could be detected in the spinal fluid of patients with ALS.ResultsToxic species of α‐Syn were detected in CSF in 18 of 127 ALS patients, 5 of whom were from Guam. Two out of twenty six samples from patients with C9orf72 variant ALS had positive seed‐amplification assay (SAAs). No positive tests were noted in superoxide dismutase type 1 ALS subjects (n = 14). The SAA was negative in 31 control subjects.ConclusionsOur findings suggest that a sub‐group of ALS occurs in which self‐replicating α‐Syn is detectable and likely contributes to its pathogenesis. This finding may have implications for the diagnosis and treatment of this disorder.

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Section: F I G U R Ementioning

confidence: 99%

Misfolded alpha‐synuclein in amyotrophic lateral sclerosis: Implications for diagnosis and treatment

Smith,

Hovren,

Bowser

et al. 2024

Euro J of Neurology

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show abstract

“…Certainly, it has not yet matured to an extent that would make it is possible to make specific recommendations (eg, by reducing exposures) to meaningfully reduce the future risk of ALS. However, experience from the transient increase in ALS incidence in Guam related to neurotoxin exposure, for example, beta-methylamino-L-alanine in the seed of cycad plants, illustrates the potential impact of environmental exposures and dramatic impact of successful mitigation efforts 35…”

Section: Higher-risk Groups For Study and Targeting Of Prevention Eff...mentioning

confidence: 99%

A roadmap to ALS prevention: strategies and priorities

Benatar

Goutman

Staats³

et al. 2023

J Neurol Neurosurg Psychiatry

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“…Parkinsonism is often a feature in patients with hexanucleotide repeat expansions in C9orf72, one of the most common genetic forms of ALS [56]. However, parkinsonism in ALS can be very variable in terms of symmetricity of body involvement, phenotypic predominance of rest tremor or other motor features, and response to dopaminergic medication [57,58].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%