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Lewy Body Pathology in Alzheimer's Disease
Abstract
Lewy bodies, the characteristic pathological lesion of substantia nigra neurons in Parkinson's disease (PD), are frequently observed to accompany the amyloid plaque and neurofibrillary tangle pathology of Alzheimer's disease (AD). However the typical anatomic distribution of Lewy bodies in AD is distinct from PD. The most common site of occurrence is the amygdala, where Lewy bodies are observed in approximately 60% of both sporadic and familial AD. Other common sites of occurrence include the periamygdaloid and entorhinal cortex, while neocortical and brainstem areas develop Lewy bodies in a lower percentage of cases. In contrast, dementia with Lewy bodies (DLB), defined by widespread neocortical and brainstem Lewy bodies but frequently accompanied by variable levels of AD-type pathology, represents the other end of a spectrum of pathology associated with dementia. The observation of Lewy bodies in familial AD cases suggests that like neurofibrillary tangles, the formation of Lewy bodies can be induced by the pathological state caused by Abeta-amyloid overproduction. The role of Lewy body formation in the dysfunction and degeneration of neurons remains unclear. The protein alpha-synuclein appears to be an important structural component of Lewy bodies, an observation spurred by the discovery of point mutations in the alpha-synuclein gene linked to rare cases of autosomal dominant PD. Further investigation of alpha-synuclein and its relationship to pathological conditions promoting Lewy body formation in AD, PD, and DLB may yield further insight into pathogenesis of these diseases.
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α-Synuclein is a protein that can accumulate in the neurons of patients with Parkinson disease.
“Other targets in neurology where a PROTAC modality may offer clear advantages over current therapeutic agents include α-synuclein, a protein that can accumulate in the neurons of patients with Parkinson disease192.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [192]
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Metadata
- Authors
- Kotzbauer, P. T., Tojanowski, J. Q., & Lee, V. M. V.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Lee, Virginia M. V.
- ORCID
- Kotzbauer, Paul T.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2001
- Volume
- 17
- Issue
- 2
- Pages
- 225-232
- ISSN
- 0895-8696 (ISSN-L)
- OpenAlex
- W2081331575
- Cited by
- 177
- References
- 82
- Citations by year
- 2026: 5 · 2025: 20 · 2024: 9 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 9 · 2012: 9
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Lewy bodies, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, alpha-synuclein, amygdala, amyloid plaques, neurofibrillary tangles, familial Alzheimer's disease, substantia nigra, entorhinal cortex, brainstem, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Nerve Tissue Proteins, Neurons, Amyloid beta-Peptides, Lewy Bodies, tau Proteins, Point Mutation, Oxidative Stress, Synucleins, alpha-Synuclein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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