Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies by immunoprecipitation.
Antibodies raised against human alpha2-6 and beta2-4 nicotinic receptor subunits were utilized to fractionate (3)H-epibatidine binding in human temporal cortex and striatum. The predominant receptor subtypes in both regions contained alpha4 and beta2 subunits. In normal cortex, 10% of binding was also associated with alpha2 subunits, whereas in the striatum, contributions by alpha6 (17%) and beta3 (23%) were observed. Minimal binding (< or =5%) was associated with alpha3. In Alzheimer's disease and dementia with Lewy bodies, cortical loss of binding was associated with reductions in alpha4 (50%, P < 0.01) and beta2 (30-38%, P < 0.05). In Parkinson's disease and dementia with Lewy bodies, striatal deficits in alpha6 (91 and 59% respectively, P < 0.01) and beta3 (72 and 75%, P < 0.05) tended to be greater than for alpha4 and beta2 (50-58%, P < 0.05). This study demonstrates distinct combinations of subunits contributing to heteromeric nicotinic receptor binding in the human brain that are area/pathway specific and differentially affected by neurodegeneration.
Gotti
Cecilia
C
CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Italy.
Moretti
Milena
M
Bohr
Iwo
I
Ziabreva
Iryna
I
Vailati
Silvia
S
Longhi
Renato
R
Riganti
Loredana
L
Gaimarri
Annalisa
A
McKeith
Ian G
IG
Perry
Robert H
RH
Aarsland
Dag
D
Larsen
Jan Petter
JP
Sher
Emanuele
E
Beattie
Ruth
R
Clementi
Francesco
F
Court
Jennifer A
JA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000595:Amino Acid Sequence; D001344:Autopsy; D003342:Corpus Striatum / Q000473:pathology*; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D013702:Temporal Lobe / Q000473:pathology*
D010446:Peptide Fragments; D011978:Receptors, Nicotinic