Journal Article DZNE-2020-05988

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In vivo staging of regional amyloid deposition.

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2017
Ovid [S.l.]

Neurology 89(20), 2031-2038 () [10.1212/WNL.0000000000004643]

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Abstract: 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.Multiregional analysis of florbetapir (18F-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.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.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.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Aging: metabolism (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Aniline Compounds (MeSH) ; Biomarkers: metabolism (MeSH) ; Cerebral Cortex: diagnostic imaging (MeSH) ; Cerebral Cortex: metabolism (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Cross-Sectional Studies (MeSH) ; Disease Progression (MeSH) ; Ethylene Glycols (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Neostriatum: diagnostic imaging (MeSH) ; Neostriatum: metabolism (MeSH) ; Peptide Fragments: cerebrospinal fluid (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Amyloid beta-Peptides ; Aniline Compounds ; Biomarkers ; Ethylene Glycols ; Peptide Fragments ; amyloid beta-protein (1-42) ; florbetapir

Classification:

Contributing Institute(s):
  1. Clinical Dementia Research Rostock /Greifswald (Clinical Dementia Research Rostock /Greifswald ; AG Teipel)
Research Program(s):
  1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2017
Database coverage:
Medline ; Allianz-Lizenz ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > ROS DZNE > ROS DZNE-AG Teipel
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 Record created 2020-02-18, last modified 2024-03-21


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