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

Lookup NU author(s): Dr Sean Colloby, Professor John O'Brien, Professor John-Paul TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 spatialcovariance 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.

Publication metadata

Author(s): Colloby SJ, Field RH, Wyper DJ, O'Brien JT, Taylor JP

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2016

Volume: 47

Pages: 83-90

Print publication date: 01/11/2016

Online publication date: 30/07/2016

Acceptance date: 22/07/2016

Date deposited: 23/09/2016

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier


DOI: 10.1016/j.neurobiolaging.2016.07.017


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Funder referenceFunder name
G9817682Medical Research Council UK
WT088441MAWellcome Trust