Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum

• Published in: Neuropathology and applied neurobiology 2016-08, Vol.42 (5), p.451-462
• Main Authors: Sierra, M., Gelpi, E., Martí, M. J., Compta, Y.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; alpha-Synuclein - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; amyloid-β; cerebellum; Cerebellum - metabolism; Cerebellum - pathology; Dementia; Female; Humans; hyperphosphorylated tau; Lewy Bodies - metabolism; Lewy Bodies - pathology; Lewy Body Disease - metabolism; Lewy Body Disease - pathology; Lewy body disorders spectrum; Male; Mesencephalon - metabolism; Mesencephalon - pathology; midbrain; Parkinson Disease - metabolism; Parkinson Disease - pathology; tau Proteins - metabolism; α-synuclein
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/nan.12308

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. Aβ deposition in the midbrain is associated with dementia in Alzheimer's disease and Lewy body disorders and the severity of Aβ and tau pathologies in the midbrain of cases with Alzheimer's disease exceeds that found in Lewy body diseases.