Neuropathologic correlates of amyloid and dopamine transporter imaging in Lewy body disease.
Aged
Aged, 80 and over
Amyloid beta-Peptides
/ metabolism
Aniline Compounds
Autopsy
Brain
/ diagnostic imaging
Cocaine
/ analogs & derivatives
Contrast Media
Dopamine Plasma Membrane Transport Proteins
/ metabolism
Female
Humans
Lewy Body Disease
/ diagnostic imaging
Male
Middle Aged
Parkinson Disease
/ diagnostic imaging
Positron-Emission Tomography
Thiazoles
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
30 07 2019
30 07 2019
Historique:
received:
04
09
2018
accepted:
14
03
2019
pubmed:
28
6
2019
medline:
7
1
2020
entrez:
28
6
2019
Statut:
ppublish
Résumé
To develop imaging biomarkers of diseases in the Lewy body spectrum and to validate these markers against postmortem neuropathologic findings. Four cognitively normal participants with Parkinson disease (PD), 4 with PD with cognitive impairments, and 10 with dementia with Lewy bodies underwent amyloid imaging with [11C]Pittsburgh compound B (PiB) and dopamine transporter (DAT) imaging with [11C]Altropane. All 18 had annual neurologic examinations. All cognitively normal participants with PD developed cognitive impairment before death. Neuropathologic examinations assessed and scored Braak Lewy bodies, Thal distribution of amyloid, Consortium to Establish a Registry for Alzheimer's Disease neuritic amyloid plaques, Braak neurofibrillary tangles, and cerebral amyloid angiopathy, as well as total amyloid plaque burden in the superior frontal, superior parietal, occipital, and inferior temporal cortical regions. PET data were expressed as the standardized uptake value ratio with cerebellar reference. Analyses accounted for the interval between imaging and autopsy. All 18 patients met neuropathologic criteria for Lewy body disease; the DAT concentration was low in each case. All patients with elevated [11C]PiB retention measured in a neocortical aggregate had β-amyloid deposits at autopsy. [11C]PiB retention significantly correlated with neuritic plaque burden and with total plaque burden. [11C]PiB retention also significantly correlated with the severity of both Braak stages of neurofibrillary tangle and Lewy body scores. Neuritic plaque burden was significantly associated with neurofibrillary tangle pathology. Antemortem [11C]Altropane PET is a sensitive measure of substantia nigra degeneration. [11C]PiB scans accurately reflect cortical amyloid deposits seen at autopsy. These findings support the use of molecular imaging in the evaluation of patients with Lewy body diseases.
Identifiants
pubmed: 31243072
pii: WNL.0000000000007855
doi: 10.1212/WNL.0000000000007855
pmc: PMC6693430
doi:
Substances chimiques
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
0
Amyloid beta-Peptides
0
Aniline Compounds
0
Contrast Media
0
Dopamine Plasma Membrane Transport Proteins
0
N-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane
0
Thiazoles
0
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e476-e484Subventions
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Informations de copyright
© 2019 American Academy of Neurology.
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