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Parkinson Disease

      This cross-section of midbrain from an older man with a neurodegenerative disease exhibits marked pallor of the substantia nigra (arrow) compared with a normal brain.
      What is the most likely diagnosis and protein abnormality?
      • a.
        Parkinson disease, α-synuclein
      • b.
        Alzheimer disease, β-amyloid
      • c.
        Frontotemporal dementia, tau
      • d.
        Amyotrophic lateral sclerosis, TDP-43 (TAR DNA-binding protein 43)
      Answer: a. Parkinson disease, α-synuclein
      Parkinson disease is characterized by bradykinesia, rigidity, stooped shuffling gate, and often resting tremor as well as nonmotor features such as anxiety, depression, and sleep disorders, among others.
      • Ahlskog J.E.
      Parkinson disease treatment in hospitals and nursing facilities: avoiding pitfalls.
      The midbrain may exhibit pallor of the substantia nigra. Microscopic neuronal inclusions called Lewy bodies, a complex accumulation of proteins including α-synuclein, play a key role in the pathogenesis.
      • Dehay B.
      • Bourdenx M.
      • Gorry P.
      • et al.
      Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations.
      On hematoxylin and eosin stain (A), Lewy bodies appear as neuronal intracytoplasmic inclusions that are roughly spherical, eosinophilic, and surrounded by a pale “halo” (arrow). Lewy bodies are highlighted by the immunohistochemical stain for α-synuclein (B).

      References

        • Ahlskog J.E.
        Parkinson disease treatment in hospitals and nursing facilities: avoiding pitfalls.
        Mayo Clin Proc. 2014; 89: 997-1003
        • Dehay B.
        • Bourdenx M.
        • Gorry P.
        • et al.
        Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations.
        Lancet Neurol. 2015; 14: 855-866