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O2‐01‐02: A New Blood Biomarker for Alzheimer's Disease: Proof of Concept in Human and in Transgenic Animal Models
Author(s) -
Sellal Francois,
Liegeois Corinne,
Michel JeanMarc,
Barry Jean
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.834
Subject(s) - genetically modified mouse , transgene , biomarker , disease , medicine , pathology , multiple sclerosis , alzheimer's disease , immunology , biology , gene , biochemistry
Background: The need of biomarkers of Alzheimer’s disease (AD) is essential for the development of therapeutic agents. Such biomarkers should be easily accessible (ie peripheral), equally significant in humans and in animal models and possibly predictive. We have developed a method based on the use of a specific fluorescent probe, which detects bound A-beta 1-42 on cellular membranes. This method was successfully applied to fresh red blood cells from transgenic animal models of AD and blood samples from AD patients. Methods: A new fluorescent probe specific for Abeta1-42 was used to evaluate the amount of bound Abeta1-42 on fresh red blood cells. A clinical study was conducted with 131 participants. Measurements were performed on samples from 68 Alzheimer’s disease patients (AD) and 37 healthy controls (HC) aged > 80. Additionally we performed measurements on 20 patients suffering from multiple sclerosis. The same protocol was also used on red blood cells from wild type and transgenic TASTPMmice aged 4 or 14 month. Results: No significant difference in the value of the spectral index between wild type and transgenic TASTPM mice aged 4 month was observed indicating that the test was negative before the development of the pathology in the transgenic model. In mice aged 14 months, when the pathology almost completely developed, our measurement was able to distinguish wild type from transgenic mice. Similar results were obtained on human samples: our test displayed a specificity of 82 % and a sensitivity of 83 % when AD patients were compared to Healthy controls and other neurodegenerative diseases. The treatment of the patients with classical symptomatic agents did not alter our measurement Conclusions: For the first time we describe a peripheral biomarker directly related to the pathology pathway and which is equally efficient in human and in animal models. This might be an essential tool for developing new disease modifiers drugs against AD.