Tau-Targeted Multifunctional Nanocomposite for Combinational Therapy of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) remains an incurable disease and lacks efficient diagnostic methods. Most AD treatments have focused on amyloid-β (Aβ) targeted therapy; however, it is time to consider the alternative theranostics due to accumulated findings of weak correlation between Aβ deposition and cognition, as well as the failures of Phase III clinical trial on Aβ targeted therapy. Recent studies have shown that the tau pathway is closely associated with clinical development of AD symptoms, which might be a potential therapeutic target. We herein construct a methylene blue (MB, a tau aggregation inhibitor) loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding affinity to hyperphosphorylated tau but also inhibits multiple key pathways of tau-associated AD pathogenesis. We demonstrate that these nanocomposites can relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing tau hyperphosphorylation, and preventing neuronal death both in vitro and in vivo. The memory deficits of AD rats are significantly rescued upon treatment with MB loaded CeNC/IONC/MSN-T807. Our results indicate that hyperphosphorylated tau-targeted multifunctional nanocomposites could be a promising therapeutic candidate for Alzheimer's disease.

Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma

“…A lzheimer's disease (AD) is the world's most common neurodegenerative disorder, causing severe cognitive decline and irreversible memory loss 1 . AD affects more than 10% of the population over the age of 65 years worldwide and the incidence of AD will increase by more than threefold within the next 50 years 2 . Currently, clinical diagnosis of AD relies largely on neuropsychological tests and neuroimaging, but the low accuracy of cognitive assessments and the high cost of brain imaging leave a large number of AD patients diagnosed late or not at all 3 .…”

Efficient Cholera Toxin B Subunit‐Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration

“…Normally, AD is hardly detected in the early stage and develops quickly, resulting in irreversible neuronal damage, dementia, and death . Currently, there is no effective clinical treatment for this disease . Due to the limitation of the blood–brain barrier (BBB), medicine cannot be effectively sent to the expected diseased region .…”

Peptide‐Modified Mo Polyoxometalate Nanoparticles Suppress Zn2+‐Induced Aβ Aggregation

“…For the delicate and complex BBB and in vivo environment, more in‐depth study and research are still needed. Accumulating evidence showed that OA produced drastic neuronal loss, induced working memory deficits and provided a useful model for the study on the pathogenetic mechanisms involved in AD . To assess the therapeutic efficiency of our nanocomposite in vivo, Peptide@Mo‐POMs was injected in the ipsilateral hippocampus 5 days after the establishment of AD model mice.…”

“…Accumulating evidence showed that OA produced drastic neuronal loss, induced working memory deficits and provided a useful model for the study on the pathogenetic mechanisms involved in AD. [35,36] To assess the therapeutic efficiency of our nanocomposite in vivo, Peptide@Mo-POMs was injected in the ipsilateral hippocampus 5 days after the establishment of AD model mice. The in vivo therapeutic efficiency was examined by Morris water maze test at 7 days post-treatment.…”