Reduced levels of Abeta 40 and Abeta 42 in brains of smoking controls and Alzheimer's patients.
The effects of nicotine on levels of Abeta 40 and Abeta 42 and nicotinic receptor binding sites were studied in brains from nonsmoking and smoking patients with Alzheimer's disease (AD) and aged-matched controls. The levels of soluble and insoluble Abeta 40 and Abeta 42 in frontal cortex and Abeta 40 in temporal cortex and hippocampus were significantly decreased in smoking AD patients compared to nonsmokers with AD. In smoking controls the levels of soluble and insoluble Abeta 40 and Abeta 42 in the frontal and temporal cortex were significantly lower than in nonsmoking controls. The binding of [(3)H]cytisine in temporal cortex was significantly increased in smokers with AD compared to nonsmokers with AD. In smoking controls [(3)H]cytisine and [(3)H]epibatidine binding were significantly increased from 1.5- to 2-fold compared to nonsmoking controls whereas binding sites for [(125)I]alpha-bungarotoxin was less up-regulated. These results indicate that selective nicotinic receptor agonists may be a novel protective therapy in AD by reducing Abeta levels as well as the loss of nicotinic receptors in AD brain.
Hellström-Lindahl
E
E
Department of Neurotec, Division of Molecular Neuropharmacology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. Ewa.Hellstom-Lindahl@neurotec.ki.se
Mousavi
M
M
Ravid
R
R
Nordberg
A
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000493:pharmacokinetics; D002038:Bungarotoxins / Q000378:metabolism / Q000493:pharmacokinetics; D003553:Cystine / Q000378:metabolism / Q000493:pharmacokinetics; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism / Q000493:pharmacokinetics; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism / Q000493:pharmacokinetics
D016229:Amyloid beta-Peptides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D010446:Peptide Fragments; D011725:Pyridines; D011978:Receptors, Nicotinic; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D014316:Tritium; D003553:Cystine; D009538:Nicotine; C082748:epibatidine