Get access

Catechols in post-mortem brain of patients with Parkinson disease

Authors

  • D. S. Goldstein,

    1. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD
    Search for more papers by this author
  • P. Sullivan,

    1. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD
    Search for more papers by this author
  • C. Holmes,

    1. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD
    Search for more papers by this author
  • I. J. Kopin,

    1. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD
    Search for more papers by this author
  • M. J. Basile,

    1. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA
    Search for more papers by this author
  • D. C. Mash

    1. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA
    Search for more papers by this author

David S. Goldstein, Clinical Neurocardiology Section, NINDS, NIH, 9000 Rockville Pike MSC-1620, Building 10 Room 5N220, Bethesda, MD 20892-1620, USA (tel.: 301 496 2103; fax: 301 402 0180; e-mail: goldsteind@ninds.nih.gov).

Abstract

Background:  Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease.

Methods:  Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end-stage Parkinson disease (= 15) and control subjects (= 14) of similar age with similar post-mortem intervals.

Results:  Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (= 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients.

Conclusions:  Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.

Ancillary