Alzheimer's disease (AD) is the most common type of dementia and it is characterized by a gradual decline in memory and cognitive function. With the aging of the world's population, its prevalence is expected to continue to grow. Currently, there are no effective therapeutics for preventing and alleviating AD.

Extracellular Tau protein has been suggested to be the primary driver of the progression of AD. It spreads through neural networks in a prion-like manner, triggering cascading neuronal damage. Although therapies targeting this protein have shown some promise in improving cognitive impairment, they have limited efficacy due to limited brain delivery and Tau-neutralizing capacity.

In a study published in Nature Biomedical Engineering, a research team led by Prof. QIU Liping from Hangzhou Institute of Medicine (HIM) of the Chinese Academy of Sciences developed a powerful system by engineering the surface of monocytes with a high affinity Tau-specific aptamer to clear extracellular Tau in the AD-afflicted brain.

Researchers demonstrated that aptamer-functionalized monocytes can actively enter and accumulate in Tau-rich brain regions such as the hippocampus and striatum in AD model mice, and efficiently phagocytose Tau in the cerebrospinal fluid.

As a result, this intervention suppressed the hyperactivation of both microglia and astrocytes, alleviated neuroinflammation, and preserved neuronal and mitochondrial integrity. Short- and long- term treatments improved the memory and spatial learning ability without inducing toxicity or behavioral side effects.

This study shows that aptamer-guided monocytes can achieve targeted delivery, effective clearance, and sustained neuroprotection in AD-afflicted brains, providing a promising strategy for the therapeutic intervention in AD.