Neuropathology of Parkinson disease

Abstract

Introduction: Parkinson's disease (PD) is characterized by bradykinesia, rigidity, postural instability and tremor. Several pathologic processes can produce this syndrome, but neurodegeneration accompanied by neuronal inclusions composed of α-synuclein (Lewy bodies) is considered the typical pathologic correlate of PD.

Methods: The neuropathologic features of PD are reviewed based upon personal experience and review of the literature. Molecular pathology of PD is summarized from cell biological and animal studies.

Results: The pathologic feature that correlates with signs and symptoms of PD is neuronal loss in the substantia nigra with dopaminergic denervation of the striatum. Neuronal degeneration in the substantia nigra preferentially affects the ventrolateral cell group that projects to posterolateral putamen and is accompanied by formation of Lewy bodies composed of aggregated α-synuclein. Some patients with PD are found at autopsy to have other pathologic processes, such as multiple system atrophy, progressive supranuclear palsy and cerebrovascular disease (vascular Parkinsonism). The peripheral autonomic nervous system is also affected. The triggering event in PD is unknown, but recent studies suggest a role for loss of nuclear membrane integrity. Once α-synuclein aggregates forms, evidence supports cell-to-cell propagation.

Conclusion: PD is a multisystem synucleinopathy caused by poorly characterized genetic and environmental factors that produces degeneration in selectively vulnerable neuronal populations.

Keywords: Lewy body; Neuropathology; Parkinson disease; α-Synuclein.

Figure 1. Frequency of neuropathologic disorders with antemortem clinical diagnosis of PD

The pie chart shows the frequency of pathologic disorders that present with Parkinsonism without dementia in the Mayo Clinic brain bank (n=132). The most common pathology is that of LBD (brainstem predominant (BLBD), transitional (TLBD) or diffuse (DLBD)). The next most frequent disorder is progressive supranuclear palsy (PSP), followed by multiple system atrophy (MSA) and vascular Parkinsonism (VaP). Corticobasal degeneration rarely presents as PD. Other rare causes of PD include nonspecific substantia nigra degeneration associated with basal ganglia pathology or with frontotemporal degeneration (with or without motor neurons disease).