Decreased density of presynaptic alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease.
The full agonist [3H]bromoxidine (UK 14304) was used to quantitate alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease. The effects of aging and human serum Cohn fraction IV on [3H]bromoxidine binding were also assessed. In patients with Alzheimer's disease, the binding capacity (Bmax) of [3H]bromoxidine was lower in the frontal cortex (37%), hypothalamus (33%), and cerebellum (52%) than in matched controls. In the hippocampus, amygdala, and head of caudate, the binding capacities (Bmax) were unchanged. Quantitative autoradiographic analyses with [3H]bromoxidine confirmed the existence of a marked reduction (55-60%) in alpha 2A-adrenoceptor density in the frontal cortex (layers I and III). In patients with dementia who did not meet neuropathological criteria for Alzheimer's disease, the density of alpha 2-adrenoceptors was unchanged. In control subjects, the density of alpha 2A-adrenoceptors in the frontal cortex showed a significant negative correlation with age at death. The inhibitory effect of human serum Cohn fraction IV on [3H]bromoxidine was very similar in control subjects and patients with Alzheimer's disease. The observed decrease in the density of brain alpha 2-adrenoceptors in Alzheimer's disease may represent direct biochemical evidence of a presynaptic location of this receptor on noradrenergic nerve terminals in the human CNS.
Department of Neurosciences, Faculty of Medicine, University of the Basque Country, Leioa, Bizkaia, Spain.
J J
JJ
Meana
F
F
Barturen
M A
MA
Garro
J A
JA
García-Sevilla
A
A
Fontán
J J
JJ
Zarranz
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000510:Alpha-Globulins / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D002102:Cadaver; D003704:Dementia / Q000378:metabolism; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012016:Reference Values; D013569:Synapses / Q000378:metabolism*; D014018:Tissue Distribution
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000510:Alpha-Globulins; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D009638:Norepinephrine