Lewy Bodies

Excerpt

Lewy bodies (LB) are protein inclusions containing disaggregated oligomers of many cellular proteins. The German neurologist named Friederich Lewy was the first physician-scientist to describe the abnormal protein deposits in 1912 in people with paralysis agitans and, later on, Parkinson disease. Dystrophic neurites (LNs) are precursors of LB and they can contain deposits of ubiquitin (Ub) and alpha-synuclein (a-Syn), formally becoming LB and accumulating in synaptic terminals and axonal processes. A-Syn, encoded by SNCA, is a protein found in presynaptic terminals and thought to have an important neurotransmission communication between neurons and neurotransmitter vesicle trafficking. Ubiquitin is a protein involved in changing proteins biochemically to target them to degradation and autophagy. The Ub is usually at the core and neurofilaments at the outermost layer. Per recent animal model studies, a mutated form of a-Syn (A30P) leads to disaggregation, transcriptional deregulation, and silencing of DNA; it also leads to the disruption of Golgi and endoplasmic reticulum, and finally it may also play a role in collagen gene transcription, a basement membrane protein that maintains the integrity of dopaminergic neurons. These cellular processes go awry in dementia with Lewy bodies (DLB) and Parkinson disease (PD). These aberrant oligomers are also present in many other neurodegenerative disorders including, Alzheimer disease (AD), striatonigral degeneration, olivopontocerebellar atrophy, and pantothenate kinase-associated neurodegeneration, but it is unknown if they share the same pathogenesis. This article focuses on DLB and PD dementia as they are the most common forms of dementia besides Alzheimer disease. The worldwide incidence of DLB is about 1% to 2% (approximately 3 to 4 per 100,000 person-years) on patients older than 65 years and about 5% of all dementia cases in those over the age of 75. For PD dementia, approximately 10% of a PD population will develop dementia annually with an overall prevalence of 31.1% in patients between 65 to 90 years old. The data concerning age at disease or dementia onset are highly variable in the literature.

The disaggregation of alpha-synuclein, Ub, and LN are a pathognomonic neuropathological finding on autopsy in patients with PD, and DLB, found in many regions within the central nervous system including the cerebral cortex, limbic cortex, substantia nigra, hippocampus. Structurally, they are single, multiple, or polymorphic. It characterizes them into two major groups: classical or cortical LB. The classifications are based on morphology, cellular components, and location within the brain. Although Lewy Bodies are implicated in many of these disorders, it is debatable whether they are a consequence of cellular damage and dysfunction within the neuro integrity or a cause itself of the clinicopathological symptoms seen in patients. This article briefly covers the different anatomical, clinical and biochemical pathologies involved with Lewy body formation. The goal is not to provide an exhaustive description of LBs, rather a snapshot that can be useful for the everyday clinician interested in the topic.