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62/100

✓ Peer-reviewed alzhub usefulness score 62 out of 100. Getting a diagnosis

Topic: Brain proteins, microglia and lab models

Plain-language summary

Parkinson's disease and dementia with Lewy bodies are currently defined by their clinical features, with α-synuclein pathology as the gold standard to establish the definitive diagnosis. We propose that, given biomarker advances enabling accurate detection of pathological α-synuclein (ie, misfolded and aggregated) in CSF using the seed amplification assay, it is time to redefine Parkinson's disease and dementia with Lewy bodies as neuronal α-synuclein disease rather than as clinical syndromes. This major shift from a clinical to a biological definition of Parkinson's disease and dementia with Lewy bodies takes advantage of the availability of tools to assess the gold standard for diagnosis of neuronal α-synuclein (n-αsyn) in human beings during life. Neuronal α-synuclein disease is defined by the presence of pathological n-αsyn species detected in vivo (S; the first biological anchor) regardless of the presence of any specific clinical syndrome. On the basis of this definition, we propose that individuals with pathological n-αsyn aggregates are at risk for dopaminergic neuronal dysfunction (D; the second biological anchor). Our biological definition establishes a staging system, the neuronal α-synuclein disease integrated staging system (NSD-ISS), rooted in the biological anchors (S and D) and the degree of functional impairment caused by clinical signs or symptoms. Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B). The presence of clinical manifestations marks the transition to stage 2 and beyond. Stage 2 is characterised by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment. A biological definition of neuronal α-synuclein disease and an NSD-ISS research framework are essential to enable interventional trials at early disease stages. The NSD-ISS will evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated. Presently, the NSD-ISS is intended for research use only; its application in the clinical setting is premature and inappropriate.

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APA 7th

Simuni, T., Chahine, L. M., Poston, K., Brumm, M., Buracchio, T., Campbell, M., et al. (2024). A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. The Lancet. Neurology. https://doi.org/10.1016/s1474-4422(23)00405-2

Vancouver

Simuni T, Chahine LM, Poston K, Brumm M, Buracchio T, Campbell M, et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. The Lancet. Neurology. 2024. doi:10.1016/s1474-4422(23)00405-2. PMID: 38267190.

BibTeX

@article{simuni2024-38267190,
  author  = {Simuni, T. and Chahine, L. M. and Poston, K. and Brumm, M. and Buracchio, T. and Campbell, M. and Chowdhury, S. and Coffey, C. and others},
  title   = {{A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research}},
  journal = {The Lancet. Neurology},
  year    = {2024},
  doi     = {10.1016/s1474-4422(23)00405-2},
  pmid    = {38267190},
  url     = {https://doi.org/10.1016/s1474-4422(23)00405-2}
}

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How to read this study

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Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Stage 2 is characterised by subtle signs or symptoms but without functional impairment.
Stages 2B-6 require both S and D and stage-specific increases in functional impairment.
A biological definition of neuronal α-synuclein disease and an NSD-ISS research framework are essential to enable interventional trials at early disease stages.
The NSD-ISS will evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.
Presently, the NSD-ISS is intended for research use only; its application in the clinical setting is premature and inappropriate.

Why it matters

This paper proposes redefining Parkinson's disease and dementia with Lewy bodies as neuronal α-synuclein disease using a biological staging system for research. It is a proposed research framework and does not report any treatment, cure, or prevention for Alzheimer's disease.

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Study details

Evidence strengthLow

How this study scored 62/100

Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (The Lancet. Neurology)
Journal's citation record	3 / 4	The Lancet Neurology: journal h-index 457 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	4 / 5	2024 — within 3 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	6 / 7	Cited 634 times (OpenAlex, 2026-10-10)
Citations per year	5 / 5	158.5 citations a year over 4 year(s) since 2024
Impact for its field and year	6 / 6	Cited 147.4× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 27 other studies in this library
Still being cited	4 / 4	Cited 632 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author KENNETH L. MAREK: h-index 81 (OpenAlex, whole career)
Institution's track record	3 / 3	National Institutes of Health: institution h-index 2,723 (OpenAlex)
Multicenter collaboration	3 / 3	OpenAlex lists 30 institution(s) in 4 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 38267190)
Free to read	0 / 2	Behind a paywall — scores zero
Total	62 / 100	—

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