title: Basal forebrain atrophy correlates with amyloid β burden in Alzheimer's disease.
abstract: The brains of patients suffering from Alzheimer's disease (AD) have three classical pathological hallmarks: amyloid-beta (Aβ) plaques, tau tangles, and neurodegeneration, including that of cholinergic neurons of the basal forebrain. However the relationship between Aβ burden and basal forebrain degeneration has not been extensively studied. To investigate this association, basal forebrain volumes were determined from magnetic resonance images of controls, subjects with amnestic mild cognitive impairment (aMCI) and AD patients enrolled in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarkers and Lifestyle (AIBL) studies. In the AIBL cohort, these volumes were correlated within groups to neocortical gray matter retention of Pittsburgh compound B (PiB) from positron emission tomography images as a measure of Aβ load. The basal forebrain volumes of AD and aMCI subjects were significantly reduced compared to those of control subjects. Anterior basal forebrain volume was significantly correlated to neocortical PiB retention in AD subjects and aMCI subjects with high Aβ burden, whereas posterior basal forebrain volume was significantly correlated to neocortical PiB retention in control subjects with high Aβ burden. Therefore this study provides new evidence for a correlation between neocortical Aβ accumulation and basal forebrain degeneration. In addition, cluster analysis showed that subjects with a whole basal forebrain volume below a determined cut-off value had a 7 times higher risk of having a worse diagnosis within ~18 months.
authors.affiliation: Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research, The University of Queensland, Brisbane, Qld 4072, Australia.
authors.forename: Georg M
authors.initials: GM
authors.lastname: Kerbler
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation, Computational Informatics, Brisbane, Qld 4029, Australia.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Fripp
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Vic. 3084, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Vic. 3084, Australia ; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Vic. 3084, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation, Computational Informatics, Brisbane, Qld 4029, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation, Computational Informatics, Brisbane, Qld 4029, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rose
authors.affiliation: Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research, The University of Queensland, Brisbane, Qld 4072, Australia.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Coulson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001284:Atrophy / Q000473:pathology; D066187:Basal Forebrain / Q000000981:diagnostic imaging / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides
keywords: 3D, 3-dimensional; AD, Alzheimer's disease; ADNI, Alzheimer's Disease Neuroimaging Initiative; AIBL, Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging; Alzheimer's disease; Amyloid; Aβ, amyloid-beta; Basal forebrain; CSF, cerebrospinal fluid; GM, gray matter; HC, healthy control; MCI, mild cognitive impairment; MNI, Montreal Neurological Institute; MPM, maximum probability maps; MPRAGE, magnetization prepared rapid gradient echo; MRI, magnetic resonance imaging; Magnetic resonance imaging; OR, odds ratio; PET; PET, positron emission tomography; PiB, Pittsburgh compound B; SPSS, statistics software package for the social sciences; SUVR, standard uptake value ratio; SyN, symmetric normalization; T1W, T1-weighted; TG-ROC, two-graph receiver operating characteristic; WM, white matter; aMCI, amnestic mild cognitive impairment