Original Article

Neuropsychopharmacology (1998) 19, 472–480. doi:10.1016/S0893-133X(98)00044-X

Loss of Dopamine D2 Receptors in Alzheimer's Disease with Parkinsonism But Not Parkinson's or Alzheimer's Disease

JN Joyce Ph.D1, AM Murray Ph.D2, HI Hurtig MD3, GL Gottlieb MD4 and JQ Trojanowski MD, Ph.D5

  1. 1Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, AZ USA
  2. 2Clinical Brain Disorders Branch, National Institute of Mental Health, Washington, DC USA
  3. 3Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  4. 4Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  5. 5Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Correspondence: Dr. Jeffrey N. Joyce, Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, POB 1278, 10515 W. Santa Fe Dr., Sun City AZ 85372, USA

Received 3 February 1998; Revised 28 April 1998; Accepted 5 May 1998

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Abstract

A significant proportion of patients with Alzheimer's disease (AD) exhibit extrapyramidal features that are referred to as parkinsonism (AD/Park) to distinguish the clinical and pathological features that differ from Parkinson's disease (PD). Previous results from this laboratory have shown that, although the presynaptic components of the dopamine (DA) system are markedly affected in AD/Park, the pathology is not similar to PD (Murray et al. 1995; Joyce et al. 1997). In the present study, we determined whether the parkinsonian symptoms in AD/Park might also reflect changes in numbers of postsynaptic DA receptors. We analyzed the binding of [125I]epidepride biding to DA D2/D3 receptors and [3H]SCH 23390 to D1 receptors by autoradiography in the striatum of six patients with PD, nine patients with AD, seven patients with AD/Park, and 14 neurologically intact control subjects. D2 receptors were reduced in the caudate and putamen of the AD/Park group (by 42 and 27% of controls, respectively) but not reduced in AD or PD. D1 receptors were elevated by 36% in the putamen of the PD group. Dopamine receptor changes are, therefore, not similar in PD, AD, and AD/Park. The elevation in D1 receptors in PD may contribute to the unwanted side effects of L-dopa treatment. The loss of D2 receptors in AD/Park, not observed in AD lacking overt parkinsonian symptomatology, may contribute to the presence of parkinsonian features and lack of responsiveness to L-dopa.

Keywords:

D2 receptor; D1 receptor; Striatum; Basal ganglia; Receptor autoradiography

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