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

Accumulating studies suggest that extracellular Tau protein spreads through neural networks in a prion-like manner, triggering cascading neuronal damage, which may be the primary driver of the progression of AD. Although therapies targeting extracellular Tau protein have shown some promise in improving cognitive impairment, their efficacy has been hampered by limited brain delivery and Tau-neutralizing capacity. Thus, there is an urgent need to develop effective treatment to address the pathological processes associated with Tau protein.

In a recent study published in Nature Biomedical Engineering, a team led by Prof. QIU Liping from Hangzhou Institute of Medicine (HIM) of the Chinese Academy of Sciences developed a potent system through 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 suppresses the hyperactivation of both microglia and astrocytes, alleviates neuroinflammation, and preserves neuronal and mitochondrial integrity. Short- and long- term treatments improved memory and spatial learning ability without inducing toxicity or behavioral side effects.

These results indicated that aptamer-guided monocytes can achieve targeted delivery, effective clearance, and sustained neuroprotection, providing a promising strategy for therapeutic intervention in Alzheimer's disease.