title: Amyloid and tau PET demonstrate region-specific associations in normal older people.
abstract: β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB-AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p<.01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates.
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: snl@berkeley.edu.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Lockhart
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; MedTech West and the Department of Psychiatry and Neurochemistry, University of Gothenburg, 413 45 Gothenburg, Sweden. Electronic address: michael.scholl@neuro.gu.se.
authors.forename: Michael
authors.initials: M
authors.lastname: Schöll
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: slbaker@lbl.gov.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Baker
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: nagehan.ayakta@gmail.com.
authors.forename: Nagehan
authors.initials: N
authors.lastname: Ayakta
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: kaitlin.swinnerton@gmail.com.
authors.forename: Kaitlin N
authors.initials: KN
authors.lastname: Swinnerton
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: rachelkb@berkeley.edu.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Bell
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: tjmellinger@berkeley.edu.
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Mellinger
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: vshah@lbl.gov.
authors.forename: Vyoma D
authors.initials: VD
authors.lastname: Shah
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: jponeil@lbl.gov.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Neil
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: mjanabi@lbl.gov.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Janabi
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: jagust@berkeley.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000814:Aniline Compounds; D002243:Carbolines; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013702:Temporal Lobe / Q000473:pathology*; D013844:Thiazoles; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002243:Carbolines; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles; D016875:tau Proteins; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
keywords: Aging; Alzheimer's disease; Amyloid; PET; Polypathology; Tau