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

Aims: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal a-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical alpha-synuclein, tau and amyloid-beta (A beta), and striatal A beta 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 alpha-synuclein, A beta and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of A beta as it represents the last b-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: alpha-synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. A beta and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of A beta), and then peaking in AD. By contrast, cerebellar A beta 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 A beta and tau pathologies in the midbrain across the LBD-spectrum were midway between controls and AD, with A beta 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.