A 62-year-old man presents with progressive tremor at rest, rigidity, and bradykinesia over 3 years. Neuroimaging and laboratory investigations are unremarkable. Which is the most common pathological hallmark seen on autopsy in idiopathic Parkinson disease?

Explanation

## Pathological Hallmark of Idiopathic Parkinson Disease **Key Point:** Lewy bodies are the defining pathological lesion in idiopathic Parkinson disease (IPD), found predominantly in the substantia nigra pars compacta (SNpc). ### Lewy Body Composition Lewy bodies are intracytoplasmic inclusions composed of: - α-synuclein (primary protein) - Ubiquitin - Neurofilament proteins ### Distribution Pattern in IPD The Braak staging system describes the progression: 1. **Stage 1–2:** Dorsal motor nucleus of vagus, olfactory bulb 2. **Stage 3–4:** Substantia nigra pars compacta (most prominent) 3. **Stage 5–6:** Spread to neocortex **High-Yield:** Loss of dopaminergic neurons in the SNpc (up to 50–70% cell loss) correlates with motor symptom onset. The SNpc is the most severely affected region and the pathological epicenter of IPD. ### Differential Pathology | Feature | Lewy Bodies (IPD) | Neurofibrillary Tangles (AD) | Pick Bodies (FTD) | |---------|-------------------|-------------------------------|-------------------| | **Protein** | α-synuclein | Hyperphosphorylated tau | Tau inclusions | | **Location** | SNpc, brainstem | Hippocampus, cortex | Frontal/temporal | | **Disease** | Parkinson disease | Alzheimer disease | Frontotemporal dementia | **Clinical Pearl:** While Lewy bodies are most prominent in the SNpc in IPD, Lewy body pathology can extend throughout the brain (Lewy body dementia spectrum), explaining cognitive and autonomic features in advanced PD. **Mnemonic:** **SNPC** = **S**ubstantia **N**igra **P**ars **C**ompacta — the hallmark site of Lewy bodies in Parkinson disease.