title: Tau and Aβ imaging, CSF measures, and cognition in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by two molecular pathologies: cerebral β-amyloidosis in the form of β-amyloid (Aβ) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Aβ could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau PET imaging agents. Clinical pathological studies have linked tau pathology closely to the onset and progression of cognitive symptoms in patients with AD. We report PET imaging of tau and Aβ in a cohort of cognitively normal older adults and those with mild AD. Multivariate analyses identified unique disease-related stereotypical spatial patterns (topographies) for deposition of tau and Aβ. These PET imaging tau and Aβ topographies were spatially distinct but correlated with disease progression. Cerebrospinal fluid measures of tau, often used to stage preclinical AD, correlated with tau deposition in the temporal lobe. Tau deposition in the temporal lobe more closely tracked dementia status and was a better predictor of cognitive performance than Aβ deposition in any region of the brain. These data support models of AD where tau pathology closely tracks changes in brain function that are responsible for the onset of early symptoms in AD.
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brier
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gordon
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Friedrichsen
authors.affiliation: Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: John
authors.initials: J
authors.lastname: McCarthy
authors.affiliation: Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Stern
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Christensen
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Owen
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aldea
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Pathology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Pathology, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA. bances@wustl.edu.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016875:tau Proteins