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Reduced striatal tyrosine hydroxylase in incidental Lewy body disease

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Abstract

Incidental Lewy body disease (ILBD) is the term used when Lewy bodies are found in the nervous system of subjects without clinically documented parkinsonism or dementia. The prevalence of ILBD in the elderly population has been estimated at between 3.8 and 30%, depending on subject age and anatomical site of sampling. It has been speculated that ILBD represents the preclinical stage of Parkinson’s disease (PD) and/or dementia with Lewy bodies (DLB). Studies of ILBD could potentially identify early diagnostic signs of these disorders. At present, however, it is impossible to know whether ILBD is a precursor to PD or DLB or is just a benign finding of normal aging. We hypothesized that, if ILBD represents an early stage of PD or DLB, it should be associated with depletion of striatal dopaminergic markers. Eleven subjects with ILBD and 27 control subjects were studied. The ILBD subjects ranged in age from 74 to 96 years (mean 86.5) while the control subjects’ age ranged from 75 to 102 years (mean 86.7). Controls and subjects did not differ in terms of age, postmortem interval, gender distribution, medical history conditions, brain weight, neuritic plaque density or Braak neurofibrillary stage. Quantitative ELISA measurement of striatal tyrosine hydroxylase (TH), the principal enzyme for dopamine synthesis, showed a 49.8% (P = 0.01) reduction in ILBD cases, as compared with control cases. The finding suggests that ILBD is not a benign condition but is likely a precursor to PD and/or DLB.

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Acknowledgments

This research is supported by grants to the Sun Health Research Institute Brain Donation Program and the Arizona Parkinson’s Disease Consortium by the Michael J. Fox Foundation for Parkinson’s Research (The Prescott Family Initiative), the Arizona Biomedical Research Commission (contracts 4001, 0011 and 05-901) and the National Institute on Aging (P30 AG19610). We thank Dr. Haru Akiyama of the Tokyo Institute of Psychiatry for donating the phospho-serine 129 antibody.

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Authors and Affiliations

  1. Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA

    Thomas Gerald Beach, Lucia I. Sue, Jeffrey B. Peirce, Jyothi Bachalakuri, Jessica E. Dalsing-Hernandez, Lih Fen Lue, Donald J. Connor, Marwan N. Sabbagh & Douglas G. Walker

  2. Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA

    Charles H. Adler & John N. Caviness

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  1. Thomas Gerald Beach
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Correspondence to Thomas Gerald Beach.

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Beach, T.G., Adler, C.H., Sue, L.I. et al. Reduced striatal tyrosine hydroxylase in incidental Lewy body disease. Acta Neuropathol 115, 445–451 (2008). https://doi.org/10.1007/s00401-007-0313-7

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