Amyloidogenic Nanoplaques in Cerebrospinal Fluid: Relationship to Amyloid Brain Uptake and Clinical Alzheimer's Disease in a Memory Clinic Cohort.
Aged
Alzheimer Disease
/ cerebrospinal fluid
Amyloid
/ cerebrospinal fluid
Biomarkers
/ cerebrospinal fluid
Brain
/ diagnostic imaging
Cohort Studies
Female
Humans
Male
Middle Aged
Nanoparticles
/ metabolism
Outpatient Clinics, Hospital
Plaque, Amyloid
/ cerebrospinal fluid
Positron-Emission Tomography
/ methods
Alzheimer’s disease
Thioflavin T
amyloid
amyloid-β peptides
amyloidogenic proteins
biomarkers
cerebrospinal fluid
fluorescence spectrometry
positron-emission tomography
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
4
8
2020
medline:
10
9
2021
entrez:
4
8
2020
Statut:
ppublish
Résumé
Aggregation of amyloid-β (Aβ) is an early pathological event in Alzheimer's disease (AD). Consequently, measures of pathogenic aggregated Aβ are attractive biomarkers for AD. Here, we use a recently developed Thioflavin-T-Fluorescence Correlation Spectroscopy (ThT-FCS) assay to quantify structured ThT-responsive protein aggregates, so-called nanoplaques, in the cerebrospinal fluid (CSF). The overall aim of this work was to assess whether ThT-FCS determined CSF nanoplaque levels could predict amyloid brain uptake as determined by 18F-Flutemetamol PET analysis. Further, we assess whether nanoplaque levels could predict clinical AD. Nanoplaque levels in the CSF from 54 memory clinic patients were compared between sub-groups classified by 18F-Flutemetamol PET as amyloid-positive or amyloid-negative, and by clinical assessment as AD or non-AD. Nanoplaque levels did not differ between amyloid groups and could not predict brain amyloid uptake. However, nanoplaque levels were significantly increased in patients with clinical AD, and were significant predictors for AD when adjusting for age, sex, cognitive function, and apolipoprotein E (APOE) genotype. The concentration of nanoplaques in the CSF differentiates patients with clinical AD from non-AD patients.
Sections du résumé
BACKGROUND
Aggregation of amyloid-β (Aβ) is an early pathological event in Alzheimer's disease (AD). Consequently, measures of pathogenic aggregated Aβ are attractive biomarkers for AD. Here, we use a recently developed Thioflavin-T-Fluorescence Correlation Spectroscopy (ThT-FCS) assay to quantify structured ThT-responsive protein aggregates, so-called nanoplaques, in the cerebrospinal fluid (CSF).
OBJECTIVE
The overall aim of this work was to assess whether ThT-FCS determined CSF nanoplaque levels could predict amyloid brain uptake as determined by 18F-Flutemetamol PET analysis. Further, we assess whether nanoplaque levels could predict clinical AD.
METHODS
Nanoplaque levels in the CSF from 54 memory clinic patients were compared between sub-groups classified by 18F-Flutemetamol PET as amyloid-positive or amyloid-negative, and by clinical assessment as AD or non-AD.
RESULTS
Nanoplaque levels did not differ between amyloid groups and could not predict brain amyloid uptake. However, nanoplaque levels were significantly increased in patients with clinical AD, and were significant predictors for AD when adjusting for age, sex, cognitive function, and apolipoprotein E (APOE) genotype.
CONCLUSION
The concentration of nanoplaques in the CSF differentiates patients with clinical AD from non-AD patients.
Identifiants
pubmed: 32741818
pii: JAD200237
doi: 10.3233/JAD-200237
pmc: PMC7592690
doi:
Substances chimiques
Amyloid
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM