Isolation and characterization of antibody fragment selective for human Alzheimer's disease brain-derived tau variants.
Alzheimer’s disease
Biomarker
Single chain antibody fragment
Tau
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
06
03
2019
revised:
23
03
2020
accepted:
15
04
2020
pubmed:
5
6
2020
medline:
30
6
2021
entrez:
5
6
2020
Statut:
ppublish
Résumé
Reagents that can selectively recognize specific toxic tau variants associated with onset and progression of Alzheimer's disease (AD) and other tauopathies can be effective diagnostic and therapeutic tools. We utilized a novel atomic force microscopy-based biopanning protocol to isolate antibody fragments (single chain variable fragments, scFvs) that selectively bind tau variants present in human AD but not cognitively normal age-matched brain tissue. We identified 6 scFvs [Alzheimer's disease tau (ADT)-1 through 6] that readily distinguished between AD and control tissue and sera samples. We utilized 3 of the scFvs (ADT-2, ADT-4, and ADT-6) to analyze longitudinal plasma samples from 50 human patients, 25 patients which converted to AD during the study and 25 that remained cognitively normal. All 3 scFvs could distinguish the AD from control samples with higher tau levels in apolipoprotein E3/3 AD cases compared to apolipoprotein E3/4. Immunohistochemical analyses of human AD brain slices indicated several but not all tau variants overlapping with phosphorylated tau staining. Several reagents also showed therapeutic potential, protecting neuronal cells against AD tau-induced toxicity.
Identifiants
pubmed: 32497877
pii: S0197-4580(20)30134-2
doi: 10.1016/j.neurobiolaging.2020.04.014
pmc: PMC7484196
mid: NIHMS1600127
pii:
doi:
Substances chimiques
Biomarkers
0
Immunoglobulin Fragments
0
Single-Chain Antibodies
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
7-14Subventions
Organisme : NIA NIH HHS
ID : R01 AG054048
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG041472
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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