Reduced striatal tyrosine hydroxylase in incidental Lewy body disease

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.

Fig 1

Brain sections from ILBD cases depicting Lewy bodies and Lewy-related neuritic pathology. a Paraffin-embedded section stained immunohistochemically for α-synuclein, showing multiple neuritic processes and Lewy bodies in the medullary dorsal motor nucleus of the vagus nerve. b A 40-µm-thick section stained with an immunoperoxidase method for α-synuclein phosphorylated at serine 129, showing multiple neuritic processes and neurons with diffusely-stained cytoplasm in the intermediate reticular zone of the pontine tegmentum. c A 40-µm-thick section stained with thioflavine S, showing a pigmented neuron of the substantia nigra pars compacta with several fluorescent intracytoplasmic Lewy bodies. d A 40-µm-thick section stained with an immunoperoxidase method for α-synuclein phosphorylated at serine 129, showing many positive neuritic processes and a single Lewy body in the entorhinal cortex

Fig 2

Graph showing the concentrations of tyrosine hydroxylase (TH), as measured by ELISA, in the striatum of ILBD and control cases. The concentrations of TH were depleted in ILBD cases to 49.8% of control levels (P = 0.01)