Researchers at the University of Leeds and Lancaster University have made a significant breakthrough in the search for new treatments for Alzheimer’s disease, identifying the enzyme PDE4B as a promising target.
Their findings were recently published in the journal Neuropsychopharmacology, offering new hope for combating this prevalent form of dementia.
Alzheimer’s disease is the most common cause of dementia and represents a significant challenge as the global population ages.
Current treatments only manage symptoms, so there is an urgent need for therapies that address the disease’s underlying causes.
The research team, building on an Australian study that linked the PDE4B gene to an increased risk of Alzheimer’s, explored the effects of reducing this enzyme’s activity in mouse models of the disease.
These specially bred mice develop amyloid plaques in their brains, mirroring one of the key features of Alzheimer’s in humans. Typically, these mice display memory deficits when navigating mazes—a standard test in neurological studies.
However, the mice with reduced PDE4B activity did not show these memory impairments, suggesting a protective effect from the enzyme reduction.
Further investigations using functional brain imaging revealed that normal Alzheimer’s model mice had reduced glucose metabolism in their brains, a common issue in Alzheimer’s patients that affects brain function. Interestingly, mice with lowered PDE4B activity maintained normal glucose metabolism levels.
The study also revealed that typical Alzheimer’s mice exhibited increased brain inflammation, another hallmark of the disease. This was significantly reduced in mice with decreased PDE4B activity, which also showed lower levels of other proteins associated with Alzheimer’s pathology.
Despite these positive changes, the reduction in PDE4B did not decrease the number of amyloid plaques, suggesting that the enzyme’s effects might be independent of this aspect of Alzheimer’s pathology.
Dr. Steven Clapcote, the lead researcher from the University of Leeds, highlighted the profound protective effects observed in the study.
“Reducing the activity of PDE4B enzyme had a profound protective effect on memory and glucose metabolism in the Alzheimer’s disease mouse model,” he stated.
This finding is particularly compelling as it suggests potential benefits beyond Alzheimer’s, possibly extending to other forms of dementia like Huntington’s disease.
Dr. Neil Dawson, a co-author from Lancaster University, emphasized the promising nature of these results. The team found that even a 27% reduction in PDE4B activity could dramatically improve memory, brain function, and inflammation levels in mice.
The next steps involve testing PDE4B inhibiting drugs in these models to assess their effectiveness and potential as Alzheimer’s treatments.
This research represents a critical step forward in the quest to understand and effectively treat Alzheimer’s disease.
By targeting PDE4B, scientists hope to develop therapeutic strategies that not only improve symptoms but also slow or halt the disease’s progression, offering real hope to millions of affected individuals and their families worldwide.
The research findings can be found in Neuropsychopharmacology.
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