Aggregation of neurofilament and alpha-synuclein proteins in Lewy bodies: implications for the pathogenesis of Parkinson disease and Lewy body dementia.

Abstract

The presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra pars compacta, as well as neuron loss and gliosis, is a diagnostic hallmark of Parkinson disease (PD), but LBs also are seen in other cortical and subcortical neurons of the PD brain. Additionally, LBs also occur in similar populations of neurons in the brains of patients with the classic clinical and pathological features of Alzheimer disease (AD). Furthermore, the presence of numerous cortical intraneuronal LBs, but only rare AD neurofibrillary tangles and senile plaques in the brains of patients with an AD-like dementia, defines a neurodegenerative disorder known as dementia with LBs (DLB). Ultrastructural examination of LBs has revealed masses of aggregated 7-to 25-nm-diameter filaments that appear similar to neurofilaments (NFs), but the precise molecular composition of LBs, including the abnormal filaments in these intracytoplasmic neuronal inclusions, remains to be clarified. Indeed, the biological significance of LBs, especially the role that they might play in the degeneration of neurons in LB disorders, is still enigmatic (Figure).