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.
Department of Physiology and Pharmacology, Faculty of Medicine, c/Cardenal Herrera Oria s/n, Santander, Spain.
J
J
Pascual
B
B
Grijalba
J A
JA
García-Sevilla
J J
JJ
Zarranz
A
A
Pazos
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