title: A spatial covariance123I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease.
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 used123I-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 underwent1235IA-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.
authors: Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK. Electronic address: sean.colloby@ncl.ac.uk.
authors: Sean J
authors: SJ
authors: Colloby
authors: Newcastle University Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors: Robert H
authors: RH
authors: Field
authors: SINAPSE, University of Glasgow, Institute of Neuroscience and Psychology, Glasgow, UK.
authors: David J
authors: DJ
authors: Wyper
authors: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors: John T
authors: JT
authors: O'Brien
authors: Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
authors: John-Paul
authors: JP
authors: Taylor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism*; D001384:Azetidines; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D008297:Male; D016548:Prosencephalon / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic / Q000378:metabolism*; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D019690:Technetium Tc 99m Exametazime
keywords: Acetylcholine; Alzheimer's disease; Cholinergic; Nicotinic; SPECT; Spatial covariance