Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease
Abstract
Lewy bodies, the histologic hallmark of Parkinson's disease (PD), are detected in the brains of about 10% of clinically normal people over the age of 60 years. When Lewy bodies are found in normal individuals, the process is sometimes referred to as incidental Lewy body disease (iLBD). The distribution of Lewy bodies in iLBD is similar to the distribution in PD, but neuronal populations vulnerable to Lewy bodies do not show significant neuronal loss in iLBD. It remains unknown if Lewy bodies in this setting represent pre-symptomatic PD or an age-related change unrelated to PD. To address this question we identified cases of iLBD and used a marker for dopaminergic and noradrenergic neurons, tyrosine hydroxylase (TH), to determine if there were changes similar to those found in PD. TH immunoreactivity in the striatum and the epicardial nerve fibers was decreased in iLBD compared to normal controls, but not to the same extent as in PD. The findings suggest that iLBD is preclinical PD and that the lack of symptoms is due to subthreshold pathology.
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It is well established that the pathological burden of diverse lesions and proteinopathies can be substantial in people who are living independently and are clinically asymptomatic.
“it is well established that the pathological burden of diverse lesions and proteinopathies can be substantial in people who are living independently and are clinically asymptomatic [103–107].”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [107]
The correlation between hallmark lesions and the presence and severity of disease is modest.
“the correlation between hallmark lesions and the presence and severity of disease is modest”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [107]
LBD observed in individuals without apparent cognitive or motor deficit may represent pre-clinical LBD.
“this may represent pre-clinical LBD [12,22,31].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [22]
Neocortical LBD is correlated with greater likelihood of cognitive impairment.
“For cases with incomplete clinical history, we note that “Neocortical LBD” is correlated with greater likelihood of cognitive impairment [1,11-13,22,31-33,38,46,49,52].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [22]
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References 45 · Cited by 364
- Authors
- Dickson, D. W., Fujishiro, H., DelleDonne, A., Menke, J., Ahmed, Z., Klos, K. J., Josephs, K. A., Frigerio, R., Burnett, M., Parisi, J. E., & Ahlskog, J. E.
- Affiliations
- Mayo Clinic (US)
- Raleigh Neurology Associates (US)
- Corresponding author
- Dickson, Dennis W.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2008-02-09
- Volume
- 115
- Issue
- 4
- Pages
- 437-444
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2004030615
- Cited by
- 364
- References
- 45
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 13 · 2023: 15 · 2022: 19 · 2021: 21 · 2020: 12 · 2019: 18 · 2018: 19 · 2017: 29 · 2016: 16 · 2015: 16 · 2014: 19 · 2013: 17 · 2012: 29
- FWCI
- 21.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- National Institute of Neurological Disorders and Stroke (P50NS040256, P50-NS40256-09)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- incidental Lewy body disease, Parkinson's disease, Lewy bodies, tyrosine hydroxylase, dopaminergic neurons, noradrenergic neurons, striatum, neuronal loss, brain aging
- MeSH terms
- Aged, Aged, 80 and over, Brain Stem, Female, Humans, Male, Myocardium, Parkinson Disease, Tyrosine 3-Monooxygenase, Incidence, Chi-Square Distribution, Cell Death, Lewy Body Disease
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