Damage to the spinal cord, peripheral, and enteric nervous systems in Parkinson's disease: Correlation of the Lewy pathology with Braak staging

• Applicant: Dr. Kelly Luise del Tredici-Braak
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 94625390

In M. Parkinson, brain lesions (Lewy pathology, LP) begin in the olfactory bulb and parasympathetic motor neurons of the lower brainstem – not, as thought earlier, in the midbrain substantia nigra. The disease process progresses in six stages caudo-rostrally through brainstem, basal mid- and forebrain nuclei, to the cortex. Initial results from four independent autopsy-controlled longitudinal studies tend to confirm the staging protocol by Braak et al. The spinal cord is also affected early, especially sympathetic motor neurons. Does LP begin in neurons of the sympathetic or parasympathetic system?Our project is two-pronged: A central nervous system (CNS) focus will aim to answer the previous question and to see if the spinal cord or brain is affected first. A peripheral and enteric nervous sytem (PNS/ENS) focus will aim to see if peripheral LP precedes LP in the CNS. Early LP has been reported in sympathetic cardiac and prostate nerves, and in plexus of the gut (ENS, s. 2.1). In nonsymptomatic/incidental cases, ENS axons with LP extend into the gastric mucosa, where LP is only micrometers from the body’s innermost surface. We will test which PNS sites, e.g. the vagal or splanchnic nerve, are hit first and use the resulting “map” to place extra-CNS LP progression in relationship to intra-CNS LP progression. Thus, we shall extend the staging protocol to the entire nervous system. Both foci have as reference point the original brain staging procedure. Finally, two recent studies postulate that a prion-like entity might have induced LP that developed in patients’ midbrain neuronal grafts years after surgery. We want to locate the other nervous system entry-points for such a putative pathogen.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Heiko Braak