Angiotensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease.
The present study assesses the binding density of the selective angiotensin converting enzyme (ACE) radioligand [3H]ceranapril in brain tissue homogenates derived from patients with Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically normal patients. Saturation studies with [3H]ceranapril identified that the specific binding (defined by captopril, 10 microM) was homogenous and of high affinity. ACE inhibitor recognition site density was higher by some 70% in the temporal cortex (Brodmann area 22) from Alzheimer's patients whereas densities were similar in frontal cortex and cerebellum when compared to control tissue. It is unknown whether this apparently selective alteration in ACE density is directly related to, or a compensatory effect of the disease, but it provides additional support for the development of compounds which interact with the central angiotensin system as novel therapies for cognitive dysfunction.
Barnes
N M
NM
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, U.K.
Cheng
C H
CH
Costall
B
B
Naylor
R J
RJ
Williams
T J
TJ
Wischik
C M
CM
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism; D002216:Captopril / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology; D006801:Humans; D008297:Male; D009943:Organophosphorus Compounds / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000378:metabolism; D013702:Temporal Lobe / Q000201:enzymology* / Q000378:metabolism; D014316:Tritium
D000806:Angiotensin-Converting Enzyme Inhibitors; D009943:Organophosphorus Compounds; D014316:Tritium; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C054518:ceronapril