α4β2-Nicotinic Receptor Binding with 5-IA in Alzheimer’s Disease: Methods of Scan Analysis
Five patients with Alzheimer’s disease and five healthy volunteers were examined by SPECT with the nicotinic receptor ligand 123I-5-IA-85380. Patients were scanned before and after 6 weeks of treatment with donepezil. Quantification by regions of interest was reliable and the optimal normalisation procedure used cerebellar ratios. We found relative reductions in 5-IA binding capacity in patients in thalamus, frontal and central regions of interest of approximately one standard deviation unit (Cohen’s d = 1). Reductions in binding after treatment with the acetylcholinesterase inhibitor donepezil of the same magnitude occurred in the brain stem. The study was clearly too small to confirm group differences, but it suggests that 5-IA can be used to examine both group differences and treatment effects in patients with Alzheimer’s disease.
KeywordsAlzheimer’s disease Dementia Nicotinic acetylcholine receptors Single photon emission tomography
This work was supported by the Gordon Small Charitable Trust and the European Commission Network of Excellence "Diagnostic Molecular Imaging" (FP6-LIFESCIHEALTH Project Reference: 512146).
- 2.Martin-Ruiz CM, Court JA, Molnar E, Lee M, Gotti C, Mamalaki A, Tsouloufis T, Tzartos S, Ballard C, Perry RH, Perry EK (1999) Alpha4 but not alpha3 and alpha7 nicotinic acetylcholine receptor subunits are lost from the temporal cortex in Alzheimer’s disease. J Neurochem 73:1635–1640PubMedCrossRefGoogle Scholar
- 3.Wevers A, Monteggia L, Nowacki S, Bloch W, Schutz U, Lindstrom J, Pereira EFR, Eisenberg H, Giacobini E, de Vos RAI, Steur ENHJ, Maelicke A, Albuquerque EX, Schroder H (1999) Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer’s disease: histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein. Eur J Neurosci 11:2551–2565PubMedCrossRefGoogle Scholar
- 7.Pimlott SL, Piggott M, Owens J, Greally E, Court JA, Jaros E, Perry RH, Perry EK, Wyper D (2004) Nicotinic acetylcholine receptor distribution in Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and vascular dementia: in vitro binding study using 5-[(125)i]-a-85380. Neuropsychopharmacology 29:108–116PubMedCrossRefGoogle Scholar
- 9.Fujita M, Seibyl JP, Vaupel DB, Tamagnan G, Early M, Zoghbi SS, Baldwin RM, Horti AG, Koren AO, Mukhin AG, Khan S, Bozkurt A, Kimes AS, London ED, Innis RB (2002) Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123I]5-I-A-85380 in healthy human subjects. Eur J Nucl Med Mol Imaging 29:183–190PubMedCrossRefGoogle Scholar
- 10.Vaupel DB, Huso D, Tella S, Horti A, Koren A, Baum I, London ED, Kimes AS (2000) Acute toxicity and safety studies of 5-I-A-85380 and 2-F-A-85380, new radiotracers for imaging nicotinic acetylcholine receptors (nAChRs). Neuroscience 26:627Google Scholar
- 13.World Health Organisation (1993) ICD-10. International classification of diseases version 10. WHO, GenevaGoogle Scholar
- 15.The Lund and Manchester Groups (1994) Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57:416–418Google Scholar
- 20.Benton AL, Hamsher K, Sivan AB (1994) Multilingual aphasia examination. AJA Associates, Iowa CityGoogle Scholar
- 21.Kaplan E, Goodglass H, Weintraub S (1983) Boston naming test. Lea and Febiger, PhiladelphiaGoogle Scholar