Oligomeric Amyloid-β Targeted Multimodal Imaging Nanoprobe for Alzheimer’s Disease Mouse Model

Amyloid-β plaques are one of the pathological hallmarks found in Alzheimer’s disease (AD) brain, which are believed to be closely related to its pathogenesis. Thus, amyloid-β species are a cardinal feature/biomarker to monitor for diagnosis of the disease and evaluate for efficacy in the drug development. Current plaque imaging in humans based on positron emission tomography (PET) is expensive and requires a radioactive tracer affording relatively low spatial resolution. Thus, PET would not be able to provide for prognosis and early diagnosis as well as a population-wise and routine screening of the disease. In contrast, magnetic resonance imaging (MRI), commonly available in clinical setting and being a powerful non-invasive and non-radiative diagnostic technique offers excellent spatio-temporal resolution and unlimited depth of tissue penetration. Therefore, it could provide a reliable and widely accepted alternative for cerebral amyloid-β species imaging. Because of its intrinsic low sensitivity, a contrast agent would often be required to enhance the specificity and image contrast of tissues/pathology of interest in MRI. On the other hand, near infrared (NIR) fluorescence imaging being highly sensitive with good penetration depth and low auto- fluorescence from biological tissues has been widely applied for imaging of cellular structure and amyloid plaques in AD mouse model despite its limitation for cerebral imaging in humans. Intriguingly, multimodality imaging can overcome the limitations of the single modal imaging, which provides complementary and expanded scope of information for more accurate disease diagnosis and pathological features investigation. Toward this end, we propose herein to develop oligomeric Aβ-specific Gd³⁺-based nanoparticle (NP) as a multimodal (MR/NIR) imaging contrast agent for in vivo detection and imaging of oligomeric Aβ species in AD mouse model for early screening and diagnosis of the disease as well as the assessment of the efficacy of potential AD drugs.

Such oligomeric Aβ-specific Gd³⁺-based NP would provide a practical and indispenable tool to visualize and monitor the pathological features of AD, particularly Aβ oligomers by NIR/MR imaging for research and drug development in AD mouse model. Furthermore, findings of this research will open up an alternative vista to develop practical MRI contrast agent for diagnosis of AD in humans.