We are currently working on investigating the neurodegeneration inclusions in postmortem human tissues from Parkinson’s patients using correlative light and electron microscopy and tomography.
Many neurodegenerative diseases such as Parkinson’s and Alzheimer’s occur in elderly (above 50 years) resulting in progressive degeneration and/or death of neuron cells. Aging is the major risk factor of neurodegenerative diseases and there are currently no available medications that prevent or reverse the neurodegeneration that causes these diseases. As research progresses, many similarities appear that relate these diseases to one another on subcellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. The different neurodegenerative disorders are characterized on light and electron microscopic levels as intracellular aggregates such as Lewy bodies (LBs) and neurofibrillary tangles (NFTs) or extracellular deposits such as amyloid plaques. The main component of LBs is believed to be conformationally modified alpha synuclein which also found in other neurodegenerative diseases known as synucleinopathies and NFTs are aggregation of hyperphosporylated tau proteins that are most commonly known as a primary marker of Alzheimer’s and present in numerous other diseases known as tauopathies. Despite the extensive research on neurodegeneration over decades, determining whether these inclusions are the cause or they are simply produced as a natural cytoprotective reaction of the brain to prevent further damage remains elusive.
The analysis of neurodegenerative aggregates on ultrastructural level will give important insight on their constituents and the possible pathways leading to the neuronal death. To that end, we employ a variety of advanced biophysical and imaging techniques including correlative light and electron microscopy and tomography, CEMOVIS, FIB/SBF/SEM, high-pressure freezing and freeze-substitution and immunogold labeling. These techniques are applied on postmortem human brain tissues.