Isolation and characterization of antibody fragment selective for human Alzheimer's disease brain-derived tau variants.
Neurobiol Aging
; 94: 7-14, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32497877
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Fragmentos de Imunoglobulinas
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Proteínas tau
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Anticorpos de Cadeia Única
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Doença de Alzheimer
Tipo de estudo:
Etiology_studies
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Guideline
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Prognostic_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos