Quantifying regional alpha-synuclein, amyloid beta, and tau accumulation in lewy body dementia

Objective: Parkinson disease (PD) is defined by the accumulation of misfolded alpha-synuclein (alpha-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid beta (A beta) and tau accumulation, occur in some LBD cases. We sought to quantify alpha-syn, A beta, and tau accumulation in neocortical, limbic, and basal ganglia regions. Methods: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble alpha-syn, A beta, and tau with recently developed sandwich ELISAs. Results: We detected a wide range of insoluble alpha-syn accumulation in LBD cases. The majority had substantial alpha-syn accumulation in most regions, and dementia severity correlated with neocortical alpha-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial A beta accumulation, although the mean A beta level in LBD was lower than in AD. The presence of A beta was associated with greater a-syn accumulation. Tau accumulation accompanied A beta in only one LBD case. Interpretation: LBD is associated with insoluble alpha-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between A beta and alpha-syn accumulation suggests a pathophysiologic relationship between these two processes.