Lewybody

Lewy bodies are abnormal intracellular protein aggregates found within neurons. They are eosinophilic inclusions composed mainly of misfolded alpha-synuclein, along with other proteins such as ubiquitin. Lewy bodies were first described by Friedrich Lewy in 1912 as distinctive inclusions in the brainstem neurons of people with Parkinson's disease. They are the pathological hallmark of Lewy body diseases, a group that includes Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD).

In Parkinson's disease, Lewy bodies are most dense in the brainstem regions such as the substantia nigra, correlating with dopaminergic neuron loss and parkinsonian motor symptoms. In DLB and PDD, Lewy bodies are more widely distributed, including cortical areas, contributing to cognitive impairment, fluctuations in attention, visual hallucinations, and other neuropsychiatric features. The pattern and spread of Lewy pathology help explain the clinical variability and progression of these conditions. Pathophysiologically, alpha-synuclein misfolding leads to oligomers and fibrils that form Lewy bodies; a prion-like propagation through neural networks is postulated. Genetic factors include variations in the SNCA gene and mutations in GBA, among others, which can influence risk and presentation.

Diagnosis is typically clinical, supported by imaging and biomarkers, with definitive confirmation requiring postmortem neuropathological examination. Treatment is symptomatic and multidisciplinary. Levodopa remains first-line for motor symptoms; cholinesterase inhibitors (e.g., rivastigmine) can help with cognitive and behavioral symptoms; memantine may be used in some cases. Antipsychotics must be used with great caution due to severe sensitivity in Lewy body disease. Nonpharmacologic approaches and management of REM sleep behavior disorder also assist overall care.