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Neuronal Nicotinic Receptor Deficits in Alzheimer Patients with the Swedish Amyloid Precursor Protein 670/671 Mutation
Author(s) -
Marutle Amelia,
Warpman Ulrika,
Bogdanovic Nenad,
Lannfelt Lars,
Nordberg Agneta
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0721161.x
Subject(s) - epibatidine , nicotinic agonist , cholinergic , nicotine , endocrinology , alzheimer's disease , amyloid precursor protein , chemistry , medicine , acetylcholine receptor , receptor , cortex (anatomy) , neuroscience , nicotinic acetylcholine receptor , biology , biochemistry , disease
Abstract : The influence of β‐amyloid on cholinergicneurotransmission was studied by measuring alterations in nicotinicacetylcholine receptors (nAChRs) in autopsy brain tissue from subjectscarrying the Swedish amyloid precursor protein (APP) 670/671 mutation.Significant reductions in numbers of nAChRs were observed in various corticalregions of the Swedish 670/671 APP mutation family subjects (‐73 to ‐87%) aswell as in sporadic Alzheimer's disease (AD) cases (‐37 to ‐57%) using thenicotinic agonists [ 3 H]epibatidine and [ 3 H]nicotine,which bind with high affinity to both α3 and α4 and to α4nAChR subtypes, respectively. Saturation binding studies with[ 3 epibatidine revealed two binding sites in the parietal cortex ofAD subjects and controls. A significant decrease in B max (‐82%) for the high‐affinity site was observed in APP 670/671 subjects with nochange in K D compared with controls (0.018 n M APP670/671 ; 0.036 n M control). The highest load of neuronal plaques(NPs) was observed in the parietal cortex of APP 670/671 brains, whereas thenumber of [ 3 H]nicotine binding sites was less impaired comparedwith other cortical brain regions. Except for a positive significantcorrelation between the number of [ 3 H]nicotine binding sites and number of NPs in the parietal cortex, no strict correlation was observed between nAChR deficits and the presence of NPs and neurofibrillary tangles, suggesting that these different processes may be closely related but not strictly dependent on each other.