Loss of high-affinity alpha 2-adrenoceptors in Alzheimer's disease: an autoradiographic study in frontal cortex and hippocampus.
We assessed, by quantitative autoradiography, the density of high-affinity alpha 2-adrenoceptors in hippocampus and frontal cortex sections from 18 patients dying with Alzheimer's disease (AD) in comparison with a control group of 13 matched cases. The full agonist [3H]bromoxidine (UK-14304) was used as a ligand. In AD brains, the specific binding of [3H]bromoxidine was markedly decreased both in frontal cortex, the reduction ranging from 55% on layer I (P less than 0.0005) to 40% loss on layers IV-VI (P less than 0.01), and in the hippocampus where the mean of alpha 2-receptor loss was 53% both for the CA1 (P less than 0.0005) and the dentate gyrus (P less than 0.005). This dramatic decrease in the density of functional, high-affinity alpha 2-adrenoceptors very probably reflects the neuronal loss described in locus coeruleus of AD brains. The important implications of these findings for the pharmacological treatment of AD are discussed.
Pascual
J
J
Department of Physiology and Pharmacology, Faculty of Medicine, c/Cardenal Herrera Oria s/n, Santander, Spain.
Grijalba
B
B
García-Sevilla
J A
JA
Zarranz
J J
JJ
Pazos
A
A
D000316:Adrenergic alpha-Agonists; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001345:Autoradiography; D001667:Binding, Competitive; D000068438:Brimonidine Tartrate; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012016:Reference Values
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate