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In vivo staging of regional amyloid deposition

2017· article· en· 452 citations· W2766782573 on OpenAlex· 10.1212/wnl.0000000000004643

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A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.

Machine scores (provisional)

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Opus teacher head0.026
GPT teacher head0.335
Teacher spread
0.310 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

OBJECTIVES: To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging of an individual's amyloid pathology. METHODS: F-AV45)-PET data was used to determine individual amyloid distribution profiles in a sample of 667 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including cognitively normal older individuals (CN) as well as patients with mild cognitive impairment and Alzheimer disease (AD) dementia. The frequency of regional amyloid positivity across CN individuals was used to construct a 4-stage model of progressing amyloid pathology, and individual distribution profiles were used to evaluate the consistency of this hierarchical stage model across the full cohort. RESULTS: According to a 4-stage model, amyloid deposition begins in temporobasal and frontomedial areas, and successively affects the remaining associative neocortex, primary sensory-motor areas and the medial temporal lobe, and finally the striatum. Amyloid deposition in these brain regions showed a highly consistent hierarchical nesting across participants, where only 2% exhibited distribution profiles that deviated from the staging scheme. The earliest in vivo amyloid stages were mostly missed by conventional dichotomous classification approaches based on global florbetapir-PET signal, but were associated with significantly reduced CSF Aβ42 levels. Advanced in vivo amyloid stages were most frequent in patients with AD and correlated with cognitive impairment in individuals without dementia. CONCLUSIONS: The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo.

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The record

Venue
Neurology
Topic
Dementia and Cognitive Impairment Research
Field
Medicine
Canadian institutions
Funders
National Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICODeutsches Zentrum für Neurodegenerative ErkrankungenH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationUniversity of California, San DiegoPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationBristol-Myers SquibbAlzheimer's AssociationFoundation for the National Institutes of Health
Keywords
Amyloid (mycology)Deposition (geology)Sequence (biology)Amyloid βIn vivoDegenerative disease
Has abstract in OpenAlex
yes