Abstract
BackgroundConsidering the high incidence of Alzheimer’s disease among the world population over the years, and the costs that the disease poses in sanitary and social terms to countries, it is necessary to develop non-invasive diagnostic tests that allow to detect early biomarkers of the disease. Within the early diagnosis methods, the development of contrast agents for magnetic resonance imaging becomes especially useful.Accumulating evidence suggests that cholesterol may play a role in the pathogenesis of Alzheimer’s disease since abnormal deposits of cholesterol surrounding senile plaques have been described in animal transgenic models and patients with Alzheimer’s disease. In vivo experiments have also shown that diet-induced hypercholesterolemia enhances intraneuronal accumulation of β-amyloid protein accompanied by microgliosis and accelerates β-amyloid deposition in brains.Presentation of the HypothesisIn the present study, we propose for the first time the synthesis of a new nanoconjugate composed of magnetic nanoparticles bound to an anti-cholesterol antibody, to detect the abnormal deposits of cholesterol observed in senile plaques in Alzheimer’s disease by magnetic resonance imaging. The nanoplatform could also reveal the decrease of cholesterol observed in neuronal plasmatic membranes associated with this pathology.Testing the HypothesisExperimental design to test the hypothesis will be done first in vitro and then in ex vivo and in vivo studies in a second stage.Implications of the HypothesisThe designed nanoplatform could therefore detect cholesterol deposits at the cerebral level. The detection of this biomarker in areas coinciding with senile plaque accumulations could provide early information on the onset and progression of Alzheimer’s disease.
Highlights
Considering the high incidence of Alzheimer’s disease among the world population over the years, and the costs that the disease poses in sanitary and social terms to countries, it is necessary to develop noninvasive diagnostic tests that allow to detect early biomarkers of the disease
Several studies have shown that the presence of an appropriate amount of cholesterol (CHO) in the neuronal plasma membrane plays a key role in protecting nerve cells against the toxicity of β-amyloid protein in Alzheimer’s disease (AD) counteracting the excessive production of this protein [1,2,3]; neurons enriched in CHO are more resistant against oxidative stress and the toxicity of β-amyloid protein [4, 5]
Mori et al [9] showed that both in humans and transgenic amyloid precursor protein (APP) mice, CHO is abnormally accumulated in mature amyloid plaques but not in diffuse or immature plaques, suggesting that CHO could play a role in the formation and progression of senile plaques
Summary
Considering the high incidence of Alzheimer’s disease among the world population over the years, and the costs that the disease poses in sanitary and social terms to countries, it is necessary to develop noninvasive diagnostic tests that allow to detect early biomarkers of the disease. In order to detect biomarkers of AD at early stages of the disease, several studies have proposed the use of functionalized magnetic iron oxide nanoparticles (MNPs) as specific contrast agents for magnetic resonance imaging (MRI) for senile plaques [13,14,15] and ferritin protein [16] detection.
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