Laminar alterations in gamma-aminobutyric acidA, muscarinic, and beta adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer's disease.
The laminar distribution of binding to a number of postsynaptic neurotransmitter receptors was assessed autoradiographically in postmortem samples of area 23a in posterior cingulate cortex from 13 Alzheimer and nine age-matched control cases. Specific binding in all Alzheimer cases was compared to that in control cases, and the following alterations were observed: reduced muscimol binding in most layers; no changes in pirenzepine binding; and elevated cyanopindolol binding in layers Ic, IIIc, and IV. The Alzheimer cases were classified further on the basis of neuronal degeneration: class 1, no neuron loss; class 2, greatest losses in layer II or III; class 3, greatest losses in layer IV; and class 4, greatest losses in layer V or VI. This classification uncovered further alterations in ligand binding patterns. First, muscimol binding was reduced in layers II and III only in class 2 cases and in layers V and VI only in class 4 cases. Second, pirenzepine binding was reduced in layers Ic, IIIa-b, and VI of class 1 cases and layers Va and VI of class 4 cases. In spite of neuron degeneration in classes 2 and 3, there was no change in pirenzepine binding in these classes. Third, elevated cyanopindolol binding occurred in classes 3 and 4, whereas classes 1 and 2 had normal levels of binding. These results suggest that cases of Alzheimer's disease express heterogeneities in neocortical pathology which are reflected in the laminar patterns of binding to postsynaptic receptors. Reductions in muscimol binding to the gamma-aminobutyric acidA receptor had the closest relationship with neuron degeneration, whereas pirenzepine binding appeared to reflect a compensation in muscarinic receptors for changes in neuron densities.
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
B A
BA
Vogt
P B
PB
Crino
L
L
Volicer
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009118:Muscimol / Q000378:metabolism; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D009118:Muscimol; D010890:Pirenzepine; C047975:cyanopindolol; D010869:Pindolol