A 62-year-old man presents with a 3-year history of progressive resting tremor, cogwheel rigidity, and bradykinesia. MRI brain is performed for diagnostic confirmation. The structure marked **A** in the diagram shows loss of the characteristic "swallow tail sign" and dorsolateral nigral hyperintensity on susceptibility-weighted imaging. Histological examination reveals cytoplasmic inclusions composed of α-synuclein within surviving neurons. Which of the following best describes the pathological hallmark of the degenerative process affecting the structure marked **A**?

Explanation

## Why Lewy bodies (α-synuclein inclusions) in dopaminergic neurons of the substantia nigra pars compacta is right The structure marked **A** is the substantia nigra pars compacta (SNpc), which contains dopaminergic neurons that degenerate in Parkinson disease. The pathognomonic histological hallmark of this degeneration is the presence of Lewy bodies — cytoplasmic inclusions composed of α-synuclein — found within surviving neurons. The clinical presentation (resting tremor, cogwheel rigidity, bradykinesia) combined with the imaging finding of loss of the "swallow tail sign" (a marker of preserved dopaminergic neuronal pigmentation on susceptibility-weighted MRI) confirms Parkinson disease affecting the SNpc. This is the defining neuropathological feature that distinguishes PD from other neurodegenerative conditions (Robbins 10e Ch 28; Harrison 21e Ch 435). ## Why each distractor is wrong - **Amyloid-β plaques and neurofibrillary tangles in the entorhinal cortex**: These are the pathological hallmarks of Alzheimer disease, not Parkinson disease. While cognitive decline can occur in advanced PD, the primary pathology in PD is Lewy bodies in the SNpc, not amyloid-β and tau tangles. - **Polyglutamine inclusions in medium spiny neurons of the striatum**: This describes Huntington disease, caused by CAG repeat expansion. Huntington presents with chorea, not Parkinsonian features, and the primary pathology is in the striatum, not the substantia nigra. - **TDP-43 cytoplasmic inclusions in motor neurons of the spinal cord**: This is characteristic of amyotrophic lateral sclerosis (ALS), which presents with upper and lower motor neuron signs, not the Parkinsonian triad. The primary site of pathology is the motor cortex and spinal cord, not the substantia nigra. **High-Yield:** Lewy bodies (α-synuclein) in the substantia nigra pars compacta = pathognomonic for Parkinson disease; loss of "swallow tail sign" on susceptibility-weighted MRI is an emerging imaging biomarker for nigral dopaminergic degeneration. [cite: Robbins 10e Ch 28; Harrison 21e Ch 435]