| The initial purpose of this thesis was to determine the pathologic seed of rapid eye movement behavior disorder (RBD) in Lewy body disease (LBD). RBD is known to be more frequent in LBD than in Alzheimer disease (AD)---80% vs. 3%, respectively. Both LBD and AD show selective cholinergic depletion and neuronal loss in particular nuclei. Lewy bodies, which are composed of a pre-synaptic protein---alpha-synuclein, are common in brainstem nuclei projecting to and from the pedunculopontine/laterodorsal tegmentum (PPN/LDT) portion of the cholinergic system, while this nucleus is known to be spared in AD. The PPN/LDT is heavily implicated in RBD based on animal lesion data, although not elucidated in humans. In this thesis, we evaluated the underlying pathologic seed of RBD by examining human tissues to denote the contribution of three main hypothesized components: location (PPN/LDT), neurotransmitter system (cholinergic), and the type of protein aggregation (alpha-synuclein). In the process of elucidating the anatomic substrate(s) of RBD, we examined how alpha-synuclein might alter levels of the rate-limiting enzyme of the cholinergic system, choline acetyltransferase. Furthermore, we examined a mouse model of LBD, to determine the feasibility of utilizing it for RBD. Lastly, we examine if there were any overall differences in larger autopsy series of cases with and without RBD. These findings could be the key to understanding the complexity of RBD within LBD, providing further mechanisms for treatment. |
