Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer's Disease.
Aged
Aged, 80 and over
Alzheimer Disease
/ cerebrospinal fluid
Amyloid beta-Peptides
/ analysis
Aniline Compounds
Apolipoprotein E4
/ genetics
Biomarkers
Brain
/ diagnostic imaging
Brain Chemistry
Carbon Radioisotopes
Female
Fluorine Radioisotopes
Fluorodeoxyglucose F18
Humans
Male
Mental Status and Dementia Tests
Middle Aged
Neprilysin
/ cerebrospinal fluid
Neuroimaging
Peptide Fragments
/ metabolism
Positron-Emission Tomography
Radiopharmaceuticals
Thiazoles
tau Proteins
/ cerebrospinal fluid
Alzheimer’s disease
Amyloid clearance
CSF-Aβ42
CSF-tau
Cerebrospinal fluid
FDG-PET
Neprilysin
Neuronal injury
Pittsburgh compound B
Positron emission tomography
Journal
Neuro-degenerative diseases
ISSN: 1660-2862
Titre abrégé: Neurodegener Dis
Pays: Switzerland
ID NLM: 101189034
Informations de publication
Date de publication:
2019
2019
Historique:
received:
02
05
2019
accepted:
06
05
2019
pubmed:
3
7
2019
medline:
25
8
2020
entrez:
3
7
2019
Statut:
ppublish
Résumé
Neprilysin (NEP) cleaves amyloid-β 1-42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer's disease patients. CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer's pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.
Sections du résumé
BACKGROUND
Neprilysin (NEP) cleaves amyloid-β 1-42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated.
METHODS
Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer's disease patients.
RESULTS
CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET.
CONCLUSIONS
Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer's pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.
Identifiants
pubmed: 31266021
pii: 000500811
doi: 10.1159/000500811
doi:
Substances chimiques
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
0
Amyloid beta-Peptides
0
Aniline Compounds
0
Apolipoprotein E4
0
Biomarkers
0
Carbon Radioisotopes
0
Carbon-11
0
Fluorine Radioisotopes
0
MAPT protein, human
0
Peptide Fragments
0
Radiopharmaceuticals
0
Thiazoles
0
amyloid beta-protein (1-42)
0
amyloid beta-protein (40-42)
0
tau Proteins
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
Neprilysin
EC 3.4.24.11
Fluorine-18
GZ5I74KB8G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
43-50Informations de copyright
© 2019 S. Karger AG, Basel.