A Sensitive and Cost-Effective Chemiluminescence ELISA for Measurement of Amyloid-β 1-42 Peptide in Human Plasma.


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
Historique:
entrez: 30 11 2020
pubmed: 1 12 2020
medline: 28 9 2021
Statut: ppublish

Résumé

Amyloid-β42 (Aβ42) is associated with plaque formation in the brain of patients with Alzheimer's disease (AD). Studies have suggested the potential utility of plasma Aβ42 levels in the diagnosis, and in longitudinal study of AD pathology. Conventional ELISAs are used to measure Aβ42 levels in plasma but are not sensitive enough to quantitate low levels. Although ultrasensitive assays like single molecule array or immunoprecipitation-mass spectrometry have been developed to quantitate plasma Aβ42 levels, the high cost of instruments and reagents limit their use. We hypothesized that a sensitive and cost-effective chemiluminescence (CL) immunoassay could be developed to detect low Aβ42 levels in human plasma. We developed a sandwich ELISA using high affinity rabbit monoclonal antibody specific to Aβ42. The sensitivity of the assay was increased using CL substrate to quantitate low levels of Aβ42 in plasma. We examined the levels in plasma from 13 AD, 25 Down syndrome (DS), and 50 elderly controls. The measurement range of the assay was 0.25 to 500 pg/ml. The limit of detection was 1 pg/ml. All AD, DS, and 45 of 50 control plasma showed measurable Aβ42 levels. This assay detects low levels of Aβ42 in plasma and does not need any expensive equipment or reagents. It offers a preferred alternative to ultrasensitive assays. Since the antibodies, peptide, and substrate are commercially available, the assay is well suited for academic or diagnostic laboratories, and has a potential for the diagnosis of AD or in clinical trials.

Sections du résumé

BACKGROUND
Amyloid-β42 (Aβ42) is associated with plaque formation in the brain of patients with Alzheimer's disease (AD). Studies have suggested the potential utility of plasma Aβ42 levels in the diagnosis, and in longitudinal study of AD pathology. Conventional ELISAs are used to measure Aβ42 levels in plasma but are not sensitive enough to quantitate low levels. Although ultrasensitive assays like single molecule array or immunoprecipitation-mass spectrometry have been developed to quantitate plasma Aβ42 levels, the high cost of instruments and reagents limit their use.
OBJECTIVE
We hypothesized that a sensitive and cost-effective chemiluminescence (CL) immunoassay could be developed to detect low Aβ42 levels in human plasma.
METHODS
We developed a sandwich ELISA using high affinity rabbit monoclonal antibody specific to Aβ42. The sensitivity of the assay was increased using CL substrate to quantitate low levels of Aβ42 in plasma. We examined the levels in plasma from 13 AD, 25 Down syndrome (DS), and 50 elderly controls.
RESULTS
The measurement range of the assay was 0.25 to 500 pg/ml. The limit of detection was 1 pg/ml. All AD, DS, and 45 of 50 control plasma showed measurable Aβ42 levels.
CONCLUSION
This assay detects low levels of Aβ42 in plasma and does not need any expensive equipment or reagents. It offers a preferred alternative to ultrasensitive assays. Since the antibodies, peptide, and substrate are commercially available, the assay is well suited for academic or diagnostic laboratories, and has a potential for the diagnosis of AD or in clinical trials.

Identifiants

pubmed: 33252086
pii: JAD200861
doi: 10.3233/JAD-200861
pmc: PMC7874530
mid: NIHMS1663751
doi:

Substances chimiques

Amyloid beta-Peptides 0
Peptide Fragments 0
amyloid beta-protein (1-42) 0

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

1237-1244

Subventions

Organisme : NIA NIH HHS
ID : P01 AG060882
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States

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Auteurs

Pankaj D Mehta (PD)

New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.

Bruce A Patrick (BA)

New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.

David L Miller (DL)

New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.

Patricia K Coyle (PK)

Department of Neurology, Stony Brook University, Stony Brook, NY, USA.

Thomas Wisniewski (T)

Center for Cognitive Neurology, New York University School of Medicine, New York, NY, USA.

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Classifications MeSH