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
a4b2 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 a4b2 and regional cerebral blood flow covariance patterns that differentiated AD from controls.
The a4b2 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.
2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license