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Title:
Pathological α-synuclein distribution in subjects with coincident Alzheimerās and Lewy body pathology | Acta Neuropathologica
Description:
We investigated the distribution patterns of Lewy body-related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcherās input in two cohorts including: Parkinson disease patients without (PD, n = 141) and with AD (PD-AD, n = 80), dementia with Lewy bodies subjects without AD (DLB, n = 13) and demented subjects with AD and LRP pathology (Dem-AD-LB, n = 308). The Dem-AD-LB group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, which are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that (1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases; (2) coincident AD pathology is associated with increased LRP in PD indicating an interaction; (3) LRP and coincident AD pathology independently predict progression to dementia in PD, and (4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization.
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Keywords {š}
pubmed, article, google, scholar, disease, pathology, central, parkinsons, cas, alzheimers, dementia, acta, lewy, lrp, neuropathol, braak, research, neurology, brain, institute, diagnosis, dois, body, toledo, neuropathological, beach, bodies, staging, clinical, assessment, neurol, aging, national, usa, subjects, coincident, access, arizona, disord, del, tredici, dickson, alphasynuclein, department, privacy, cookies, content, distribution, december, lee,
Topics {āļø}
month download article/chapter pathological α-synuclein distribution dem-ad-lb group presented dem-ad-lb shows dem-ad-lb group central cholinergic integrity data-driven clustering approach lewy body-related pathology full article pdf dem-ad-lb body donation program coincident neuropathological diseases privacy choices/manage cookies alpha-synuclein pathology lewy bodies subjects article toledo lewy body pathology lewy body variant lewy-related pathology toledo jb clinico-pathological study disease core center lewy body disorders brain pathology related beach tg cerad neuropathology protocol pallavi gopal pennsylvania medical center coincident ad pathology consensus recommendations transgenic mouse brain author information authors article log nervous system pathology european economic area substantia nigra cells dopamine active transporter jansen steur en cingulate island sign pdd boundary issues dorsal root ganglia dickson dw disease-related pathology invited article conditions privacy policy beta-amyloid morphotypes beta-amyloid fibrils negligible brainstem pathology multimodal biomarker correlates population-based cohort
Questions {ā}
- Aarsland D, Ballard CG, Halliday G (2004) Are Parkinsonās disease with dementia and dementia with Lewy bodies the same entity?
- Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T et al (2014) Time to redefine PD?
- Tsuboi Y, Dickson DW (2005) Dementia with Lewy bodies and Parkinsonās disease with dementia: are they different?
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headline:Pathological α-synuclein distribution in subjects with coincident Alzheimerās and Lewy body pathology
description:We investigated the distribution patterns of Lewy body-related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcherās input in two cohorts including: Parkinson disease patients without (PD, nĀ =Ā 141) and with AD (PD-AD, nĀ =Ā 80), dementia with Lewy bodies subjects without AD (DLB, nĀ =Ā 13) and demented subjects with AD and LRP pathology (Dem-AD-LB, nĀ =Ā 308). The Dem-AD-LB group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, which are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that (1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases; (2) coincident AD pathology is associated with increased LRP in PD indicating an interaction; (3) LRP and coincident AD pathology independently predict progression to dementia in PD, and (4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization.
datePublished:2015-12-31T00:00:00Z
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Parkinson disease
Dementia with Lewy bodies
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Diagnosis
Classification
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Neurosciences
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headline:Pathological α-synuclein distribution in subjects with coincident Alzheimerās and Lewy body pathology
description:We investigated the distribution patterns of Lewy body-related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcherās input in two cohorts including: Parkinson disease patients without (PD, nĀ =Ā 141) and with AD (PD-AD, nĀ =Ā 80), dementia with Lewy bodies subjects without AD (DLB, nĀ =Ā 13) and demented subjects with AD and LRP pathology (Dem-AD-LB, nĀ =Ā 308). The Dem-AD-LB group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, which are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that (1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases; (2) coincident AD pathology is associated with increased LRP in PD indicating an interaction; (3) LRP and coincident AD pathology independently predict progression to dementia in PD, and (4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization.
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Parkinson disease
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name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Clinical Neuroanatomy and Neurology, University of Ulm, Ulm, Germany
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania, Philadelphia, USA
name:Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
name:Philadelphia VA Medical Center, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
name:Department of Neurology, Mayo Clinic, Scottsdale, USA
name:Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA
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