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

NEUROBIOLOGY OF AGING

卷:47

Article

Colloby, Sean J.¹  Field, Robert H.²  Wyper, David J.³  O'Brien, John T.⁴  Taylor, John-Paul¹ 

[1] Newcastle Univ, Inst Neurosci, Campus Ageing & Vitality, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

[2] Newcastle Univ, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England

[3] Univ Glasgow, SINAPSE, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland

[4] Univ Cambridge, Dept Psychiat, Cambridge, England

关键词: Alzheimer's disease;    Cholinergic;    Acetylcholine;    Nicotinic;    Spatial covariance;    SPECT;   

DOI  :  10.1016/j.neurobiolaging.2016.07.017

来源: Elsevier

【 摘 要 】

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 I-123-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine ((123)5IA-85380) single photon emission computed tomography to investigate spatial covariance of alpha 4 beta 2 nicotinic acetylcholine receptors in AD and healthy controls. Thirteen AD and 16 controls underwent 1235IA-85380 and regional cerebral blood flow ((99)mTc-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 alpha 4 beta 2 and regional cerebral blood flow covariance patterns that differentiated AD from controls. The alpha 4 beta 2 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. (C) 2016 The Authors. Published by Elsevier Inc.

【 授权许可】

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