Some patients with neurodegenerative disease may develop significant difficulty with balance, rigidity, tremor or gait. The major diseases in this category are Parkinson’s disease (PD), Parkinson’s disease with Dementia (PDD) and Dementia with Lewy bodies (DLB). These related conditions are collectively known as “synucleinopathies” or “Lewy body spectrum disorders.” This is because the characteristic neuronal inclusions (“Lewy bodies”) seen at autopsy in these disorders are primarily composed of the protein, alpha-synuclein, and these inclusions were first observed by Frederic Lewy. Alpha-synuclein is normally located at the synapse, or terminal ending, of a neuron and is involved in transporting neurotransmitters within neurons, among other functions. For unclear reasons, this protein can become misfolded and collect into inclusion bodies, resulting in neuronal loss and gliosis (a process leading to scarring) in areas of the brain and brainstem involved in balance, movement and cognition. This folding can affect the cells containing the neurotransmitter dopamine, resulting in the clinical syndromes of PD, PDD and DLB.
These motor symptoms can also occur in Frontotemporal degeneration (FTD) and Alzheimer’s disease (AD), although usually to a lesser degree. Like FTD and AD, there is no way to be certain of the underlying diagnosis of the “Lewy body disorders” without microscopic analysis of brain tissue at autopsy. The Penn FTD Center is actively involved in research for clinical, biofluid and neuroimaging biomarkers of synucleinopathies that will one day help physicians better identify and treat these disorders.