title: Spatially distinct atrophy is linked to β-amyloid and tau in preclinical Alzheimer disease.
abstract: OBJECTIVE
  To determine whether an MRI-based Alzheimer disease (AD) signature biomarker can detect tau-related neurodegeneration in preclinical AD, and to assess whether AD signature cortical thinning is associated with cognitive changes in cognitively normal (CN) older individuals.
  
  
  METHODS
  In a large cohort of CN individuals (n = 188), we measured the hippocampal volume and cortical thickness within independently defined AD signature regions. We cross-sectionally assessed the associations between AD signature cortical thinning or hippocampal atrophy with CSF biomarkers of tau (increased tau) and β-amyloid (Aβ) (decreased Aβ42). We also examined the impact of AD signature cortical thinning or other biomarker changes (i.e., hippocampal atrophy, reduced CSF Aβ42, or increased CSF tau) on cognitive performance in CN individuals.
  
  
  RESULTS
  Elevated CSF tau was associated with AD signature cortical thinning but not hippocampal atrophy. In contrast, decreased CSF Aβ42 was associated with hippocampal loss but not AD signature cortical thinning. In addition, AD signature cortical thinning was associated with lower visuospatial performance. Reduced CSF Aβ42 was related to poorer performance on episodic memory.
  
  
  CONCLUSIONS
  Spatially distinct neurodegeneration is associated with Aβ and tau pathology in preclinical AD. Aβ deposition and AD signature cortical atrophy independently affect cognition in CN older individuals.
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Tammie L
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Tyler
authors.initials: T
authors.lastname: Blazey
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Christopher
authors.initials: C
authors.lastname: Owen
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO. 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 / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D062706:Prodromal Symptoms; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins