Specifically Labeling Amyloid Plaques In Vivo At Early Stage Of Alzheimer's Disease In APP/PS1 Mice With Targeted Nano-iron Contrast Agent

BackgroundAlzheimer Disease(AD) is a slowly progressive neurodegenerative disorder whose incidences increase exponentially with age, and the increasing number of people with dementia is a great challenge for society and health-care systems. At present, the pathogenesis of Alzheimer's disease is still unclear and there are also no effective diagnosis or treatment methods. Since the primary diagnosis of AD is still based on autopsy, biopsy and clinical neuropsychometric testing, improved methods for early diagnosis and measures of disease progression are needed and have the very vital significance. Direct detection of amyloid plaque in vivo in Alzheimer's disease (AD) with specific nano magnetic biomarkers that can selectively mark the senile plaques is expected to be useful for early diagnosis of AD.ObjectiveDirect detection of amyloid plaque in vivo in Alzheimer's disease (AD) with specific nano magnetic biomarkers that can selectively mark the senile plaques to diagnosis AD.MethodsTo synthesis a specifically "targeted nano-iron contrast agent" with the dextran-coated ultra-small superparamagnetic iron oxide (USPIO) particle, which binds to Aβ1-40 peptide and Tat-PTD (Tat-protein transduction domain). Then this agent was injected into the APP/PS1 mice and detected whether it could cross the BBB and specifically label the amyloid plaques in the AD brain in vivo. And the correlation between MRI results and the histological stainings was done in the end.Results1. The Tat-PTD moiety in the compound eventually took the nano-iron contrast agent into the living cells.2. The nano-iron contrast agent does have the ability to accelerate T2 relaxation rates of water protons in the cells and to negatively reinforce the T2 signal intensity in the labeled cells.3. After injection of the targeted nano-iron contrast agent, plaques could be detected in vivo in as young as 9-month-old APP/PS1 mice by MRI.4. Thioflavin S stained and iron-stained images have been precisely and spatially registered over a circumscribed area of the cortex.ConclusionThis special targeted nano contrast agent enables the early detection of plaques by MRI and can be further applied in the studies of early diagnosis of AD.Innovation pointsThis study provides a method for selectively detecting Aβin AD transgenic mice in vivo without injection of mannitol in advance to open the blood-brain barrier (BBB) and suggests that targeted nano contrast agent enables the early detection of plaques by MRI and can be further applied in the studies of early diagnosis of AD. Moreover, nanoparticles may also be used as selective biomarkers for detecting the location and removal of other amyloid plaques derived from different amyloidogenic proteins that lead to neurodegenerative diseases such as Parkinson's, Huntington's and prion diseases.