A spatial covariance (123)I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease

Colloby, S. J., Field, R. H., Wyper, D. J., O'Brien, J. T. and Taylor, J.-P. (2016) A spatial covariance (123)I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease. Neurobiology of Aging, 47, pp. 83-90. (doi: 10.1016/j.neurobiolaging.2016.07.017) (PMID:27565302)

Abstract

Alzheimer's disease (AD) is characterized by widespread degeneration of cholinergic neurons, particularly in the basal forebrain. However, the pattern of these deficits and relationship with known brain networks is unknown. In this study, we sought to clarify this and used 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (1235IA-85380) single photon emission computed tomography to investigate spatial covariance of α4β2 nicotinic acetylcholine receptors in AD and healthy controls. Thirteen AD and 16 controls underwent 1235IA-85380 and regional cerebral blood flow (99mTc-exametazime) single photon emission computed tomography scanning. We applied voxel principal component (PC) analysis, generating series of principal component images representing common intercorrelated voxels across subjects. Linear regression generated specific α4β2 and regional cerebral blood flow covariance patterns that differentiated AD from controls. The α4β2 pattern showed relative decreased uptake in numerous brain regions implicating several networks including default mode, salience, and Papez hubs. Thus, as well as basal forebrain and brainstem cholinergic system dysfunction, cholinergic deficits mediated through nicotinic acetylcholine receptors could be evident within key networks in AD. These findings may be important for the pathophysiology of AD and its associated cognitive and behavioral phenotypes.

• Item Type: Articles
• Additional Information: The authors thank the Alzheimer’s Society, the Newcastle Healthcare Charity, the Medical Research Council UK (grant number G9817682), the National Institute for Health Research (NIHR) for Public Benefit, Wellcome Trust (WT088441MA Fellowship funding John-Paul Taylor), NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust, the University of Cambridge, The NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease, and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wyper, Professor David
• Authors: Colloby, S. J., Field, R. H., Wyper, D. J., O'Brien, J. T., and Taylor, J.-P.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Science and Engineering > School of Physics and Astronomy
• Journal Name: Neurobiology of Aging
• Publisher: Elsevier
• ISSN: 0197-4580
• Published Online: 30 July 2016
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Neurobiology of Aging 47: 83-90
• Publisher Policy: Reproduced under a Creative Commons License