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Adrenergic Receptors in Aging and Alzheimer's Disease: Increased β 2 ‐Receptors in Prefrontal Cortex and Hippocampus
Author(s) -
Kalaria R. N.,
Andorn A. C.,
Tabaton M.,
Whitehouse P. J.,
Harik S. I.,
Unnerstall J. R.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb09242.x
Subject(s) - locus ceruleus , endocrinology , medicine , receptor , prefrontal cortex , hippocampus , adrenergic receptor , locus coeruleus , alzheimer's disease , putamen , chemistry , neuroscience , biology , central nervous system , dopamine , cognition , dopaminergic , substantia nigra , disease
Loss of pigmented noradrenergic locus ceruleus neurons occurs in Alzheimer's disease (AD) and, to a lesser extent, in aging. We studied β‐adrenergic receptors and their subtypes, β 1 and β 2 , by the specific binding of 125 I‐pindolol to particulate membrane preparations from prefrontal cortex, hippocampus, putamen, and cerebellum and to sections from frontal cortex by in vitro autoradiography. In prefrontal cortex from controls, numbers of total β‐ and β‐adrenoceptors did not significantly correlate with age, but number of β 1 ‐adrenoceptors showed a weak but significant negative correlation. Binding in tissue particulate preparations to total β‐receptors did not reveal significant differences in samples from prefrontal cortex between AD subjects and age‐matched controls. However, β 1 ‐adrenoceptors were decreased and β 2 ‐adrenoceptors were increased in number by ∼30‐50% in AD subjects. Thus, the relative ratio of β/β 2 ‐receptors was decreased in AD. Binding by in vitro receptor autoradiography performed in a subset of samples of frontal cortex also showed β 2 ‐adrenoceptors, and less consistently total β‐and β 1 recep‐tors, to be increased significantly in number in cortical laminae II, III, IV, and V of tissue sections from AD subjects. In these subjects, number of locus ceruleus cells and norepinephrine concentrations in putamen and frontal cortex were markedly reduced compared with values in controls. In the hippocampus, total β‐ and both β 2 ‐ and β 1 ‐adrenoceptors were increased in number in AD. In contrast, in the putamen. where β‐receptors predominate, total β‐ and β 1 ‐receptors were significantly decreased in number with no consistent change in content of β 2 ‐receptors in AD. There were no significant changes in the cerebellum. Specific pindolol binding was not affected by interval between death and sampling of tissue at autopsy. Our results indicate selective changes in number of β‐receptors in AD. These changes in the cortex and hippocampus suggest receptor upregulation in response to noradrenergic deafferentation from the locus ceruleus or may simply reflect glial proliferation in AD.