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Alzheimer’s Gene Discovery Offers Hope For Preventive Therapy

’s disease is the most common neurodegenerative disorder, affecting more than five million Americans, but currently there is no way to prevent, delay or stop its progression. A study published online by the Cell Press journal Neuron shows that a gene called CD33 contributes to Alzheimer’s disease by inhibiting the ability of immune cells to remove toxic molecules in the brain. The findings provide new insights into the molecular causes of the disease and reveal a novel potential therapy that could prevent cognitive decline and brain damage at early stages.

“Before our study, nothing was known about the function of CD33 in the brain,” says senior study author of Massachusetts General Hospital and Harvard Medical School. “Moreover, our findings suggest that pharmaceutical inactivation of CD33 represents a potentially powerful new therapy for the treatment and prevention of Alzheimer’s disease, and perhaps other neurodegenerative disorders.”

One hallmark of Alzheimer’s disease is the formation of beta-amyloid plaques – deposits of toxic molecules between neurons in the brain. Past studies have suggested that these plaques cause neurons to die, leading to cognitive deficits such as impaired memory. Although several genes – including CD33 – have recently been implicated in Alzheimer’s disease, little is known about how they regulate the formation of beta-amyloid plaques and contribute to disease progression.

In the new study, Tanzi and his team found that CD33 is active in microglia – immune cells that clean up debris and destroy pathogens in the brain. In brain tissue samples from deceased individuals who had Alzheimer’s disease, higher levels of CD33 activity in microglia were associated with an increased number of beta-amyloid plaques. Inactivation of the CD33 gene in mice enhanced the ability of microglia to clear up toxic beta-amyloid molecules in the brain. Similarly, inactivation of the CD33 gene in a mouse model of Alzheimer’s disease reduced the number of beta-amyloid plaques in the brain.

“This is the first time that we have direct evidence of a gene, CD33, that directly controls beta-amyloid clearance by microglia,” Tanzi says. “Our findings raise the exciting possibility that the inability of microglia to degrade beta-amyloid in Alzheimer’s disease could be reversed therapeutically by inhibition of CD33 activity.”


Neuron, Griciuc et al.: “Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta.”
Cell Press