Nerve growth factor (NGF) pathway biomarkers in Down syndrome prior to and after the onset of clinical Alzheimer's disease: A paired CSF and plasma study.
Adult
Alzheimer Disease
/ blood
Biomarkers
/ blood
Brain
/ physiopathology
Down Syndrome
/ complications
Female
Humans
Male
Matrix Metalloproteinase 3
/ blood
Matrix Metalloproteinase 9
/ blood
Middle Aged
Nerve Growth Factor
/ metabolism
Neuropeptides
/ blood
Serpins
/ blood
Signal Transduction
tau Proteins
/ metabolism
Neuroserpin
Alzheimer's disease
Down syndrome
MMP-1
MMP-3
MMP-9
NGF metabolic pathway
biomarkers
blood
cerebrospinal fluid
cholinergic
metalloproteases
nerve growth factor
neuroserpin
plasma
proNGF
tissue plasminogen activator
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
28
07
2020
received:
30
03
2020
accepted:
05
10
2020
pubmed:
24
11
2020
medline:
4
11
2021
entrez:
23
11
2020
Statut:
ppublish
Résumé
The discovery that nerve growth factor (NGF) metabolism is altered in Down syndrome (DS) and Alzheimer's disease (AD) brains offered a framework for the identification of novel biomarkers signalling NGF deregulation in AD pathology. We examined levels of NGF pathway proteins (proNGF, neuroserpin, tissue plasminogen activator [tPA], and metalloproteases [MMP]) in matched cerebrospinal fluid (CSF)/plasma samples from AD-symptomatic (DSAD) and AD-asymptomatic (aDS) individuals with DS, as well as controls (HC). ProNGF and MMP-3 were elevated while tPA was decreased in plasma from individuals with DS. CSF from individuals with DS showed elevated proNGF, neuroserpin, MMP-3, and MMP-9. ProNGF and MMP-9 in CSF differentiated DSAD from aDS (area under the curve = 0.86, 0.87). NGF pathway markers associated with CSF amyloid beta and tau and differed by sex. Brain NGF metabolism changes can be monitored in plasma and CSF, supporting relevance in AD pathology. These markers could assist staging, subtyping, or precision medicine for AD in DS.
Sections du résumé
BACKGROUND
The discovery that nerve growth factor (NGF) metabolism is altered in Down syndrome (DS) and Alzheimer's disease (AD) brains offered a framework for the identification of novel biomarkers signalling NGF deregulation in AD pathology.
METHODS
We examined levels of NGF pathway proteins (proNGF, neuroserpin, tissue plasminogen activator [tPA], and metalloproteases [MMP]) in matched cerebrospinal fluid (CSF)/plasma samples from AD-symptomatic (DSAD) and AD-asymptomatic (aDS) individuals with DS, as well as controls (HC).
RESULTS
ProNGF and MMP-3 were elevated while tPA was decreased in plasma from individuals with DS. CSF from individuals with DS showed elevated proNGF, neuroserpin, MMP-3, and MMP-9. ProNGF and MMP-9 in CSF differentiated DSAD from aDS (area under the curve = 0.86, 0.87). NGF pathway markers associated with CSF amyloid beta and tau and differed by sex.
DISCUSSION
Brain NGF metabolism changes can be monitored in plasma and CSF, supporting relevance in AD pathology. These markers could assist staging, subtyping, or precision medicine for AD in DS.
Identifiants
pubmed: 33226181
doi: 10.1002/alz.12229
pmc: PMC8043977
mid: NIHMS1640804
doi:
Substances chimiques
Biomarkers
0
Neuropeptides
0
Serpins
0
tau Proteins
0
Nerve Growth Factor
9061-61-4
MMP3 protein, human
EC 3.4.24.17
Matrix Metalloproteinase 3
EC 3.4.24.17
Matrix Metalloproteinase 9
EC 3.4.24.35
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
605-617Subventions
Organisme : NIA NIH HHS
ID : RF1 AG061566
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG056850
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG056974
Pays : United States
Informations de copyright
© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
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