Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort.
Aged
Alzheimer Disease
/ blood
Apolipoprotein E4
/ genetics
Biomarkers
/ blood
Blood Proteins
/ analysis
Body Burden
Cerebral Amyloid Angiopathy
/ blood
Cognitive Dysfunction
/ blood
Cohort Studies
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Positron-Emission Tomography
Proteomics
ROC Curve
tau Proteins
/ cerebrospinal fluid
Alzheimer’s disease
amyloid-β
biomarkers
plasma
proteomics
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:
28
1
2020
medline:
14
5
2021
entrez:
28
1
2020
Statut:
ppublish
Résumé
We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.
Identifiants
pubmed: 31985466
pii: JAD190434
doi: 10.3233/JAD-190434
pmc: PMC7175945
doi:
Substances chimiques
Apolipoprotein E4
0
Biomarkers
0
Blood Proteins
0
MAPT protein, human
0
tau Proteins
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
213-225Subventions
Organisme : Wellcome Trust
ID : 104025/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17215
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
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