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Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum.
Neuropathol Appl Neurobiol. 2016 08; 42(5):451-62.NA

Abstract

AIMS

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal α-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical α-synuclein, tau and amyloid-β (Aβ), and striatal Aβ aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution. We aimed to assess these pathologies further down the encephalon across the LBD-spectrum.

METHODS

Semiquantitative rating of α-synuclein, Aβ and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of Aβ as it represents the last β-amyloidosis stage) sections from cases representative of the LBD-spectrum (PD non-dementia, PD-dementia, DLB; n = 10 each) compared to controls (n = 10) and Alzheimer's disease (AD; n = 10).

RESULTS

α-synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. Aβ and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of Aβ), and then peaking in AD. By contrast, cerebellar Aβ scores were marginal across the LBD-spectrum, as opposed to AD, only showing a trend towards greater involvement in LBD cases with dementia.

CONCLUSIONS

Frequency and severity of Aβ and tau pathologies in the midbrain across the LBD-spectrum were midway between controls and AD, with Aβ in the tectum/tegmentum being associated with dementia. These findings might have potential implications in the eventual interpretation of regional uptake of in vivo molecular imaging of these pathologies.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Sierra M
Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain. Service of Neurology, Hospital Universitario Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Cantabria, Spain.
Gelpi E
Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Catalonia, Spain.
Martí MJ
Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.
Compta Y
Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.

MeSH

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesCerebellumFemaleHumansLewy BodiesLewy Body DiseaseMaleMesencephalonParkinson Diseasealpha-Synucleintau Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26810462

Citation

Sierra, M, et al. "Lewy- and Alzheimer-type Pathologies in Midbrain and Cerebellum Across the Lewy Body Disorders Spectrum." Neuropathology and Applied Neurobiology, vol. 42, no. 5, 2016, pp. 451-62.
Sierra M, Gelpi E, Martí MJ, et al. Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum. Neuropathol Appl Neurobiol. 2016;42(5):451-62.
Sierra, M., Gelpi, E., Martí, M. J., & Compta, Y. (2016). Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum. Neuropathology and Applied Neurobiology, 42(5), 451-62. https://doi.org/10.1111/nan.12308
Sierra M, et al. Lewy- and Alzheimer-type Pathologies in Midbrain and Cerebellum Across the Lewy Body Disorders Spectrum. Neuropathol Appl Neurobiol. 2016;42(5):451-62. PubMed PMID: 26810462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum. AU - Sierra,M, AU - Gelpi,E, AU - Martí,M J, AU - Compta,Y, Y1 - 2016/04/01/ PY - 2015/08/11/received PY - 2016/01/08/revised PY - 2016/01/26/accepted PY - 2016/1/27/entrez PY - 2016/1/27/pubmed PY - 2017/12/5/medline KW - Lewy body disorders spectrum KW - amyloid-β KW - cerebellum KW - hyperphosphorylated tau KW - midbrain KW - α-synuclein SP - 451 EP - 62 JF - Neuropathology and applied neurobiology JO - Neuropathol Appl Neurobiol VL - 42 IS - 5 N2 - AIMS: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal α-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical α-synuclein, tau and amyloid-β (Aβ), and striatal Aβ aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution. We aimed to assess these pathologies further down the encephalon across the LBD-spectrum. METHODS: Semiquantitative rating of α-synuclein, Aβ and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of Aβ as it represents the last β-amyloidosis stage) sections from cases representative of the LBD-spectrum (PD non-dementia, PD-dementia, DLB; n = 10 each) compared to controls (n = 10) and Alzheimer's disease (AD; n = 10). RESULTS: α-synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. Aβ and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of Aβ), and then peaking in AD. By contrast, cerebellar Aβ scores were marginal across the LBD-spectrum, as opposed to AD, only showing a trend towards greater involvement in LBD cases with dementia. CONCLUSIONS: Frequency and severity of Aβ and tau pathologies in the midbrain across the LBD-spectrum were midway between controls and AD, with Aβ in the tectum/tegmentum being associated with dementia. These findings might have potential implications in the eventual interpretation of regional uptake of in vivo molecular imaging of these pathologies. SN - 1365-2990 UR - https://www.unboundmedicine.com/medline/citation/26810462/Lewy__and_Alzheimer_type_pathologies_in_midbrain_and_cerebellum_across_the_Lewy_body_disorders_spectrum_ DB - PRIME DP - Unbound Medicine ER -