Neuropathology of incidental Lewy body & prodromal Parkinson's disease

• Published in: Molecular neurodegeneration Vol. 18; no. 1; p. 32
• Main Authors: Koeglsperger, Thomas, Rumpf, Svenja-Lotta, Schließer, Patricia, Struebing, Felix L, Brendel, Matthias, Levin, Johannes, Trenkwalder, Claudia, Höglinger, Günter U, Herms, Jochen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.05.2023; BioMed Central; BMC
• Subjects: alpha-Synuclein; Alzheimer's disease; Apoptosis; Brain research; Dementia; Dopamine receptors; Enteric nervous system (ENS); Health aspects; Humans; Incidental Lewy body disease (iLBD); Lewy bodies; Lewy Bodies - pathology; Lewy body disease; Lewy Body Disease - pathology; Lewy body α-Synuclein; Literature reviews; Medical research; Medicine, Experimental; Microscopy; Movement disorders; Mutation; Nerve Degeneration - pathology; Neurodegenerative diseases; Neurons; Neuropathology; Parkinson Disease - pathology; Parkinson's disease; Pathology; Physiological aspects; Prodromal Parkinson’s disease (PD); Proteins; REM-sleep behaviour disorder (RBD); Review; REM-sleep behaviour disorder (RBD); Lewy body α-Synuclein; Incidental Lewy body disease (iLBD); Prodromal Parkinson’s disease (PD); Enteric nervous system (ENS)
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-023-00622-7

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing. Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD. Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons. Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.