Researchers have identified a gene that, when inhibited, could protect against the symptoms of Alzheimer’s disease in mice, which could pave the way for new treatments.
- While the number of people diagnosed with Alzheimer’s disease is expected to double by 2050, a team of scientists has uncovered a new potential target for treating the neurodegenerative pathology: the PDE4B gene.
- Building on previous work that identified this gene as a risk factor for Alzheimer’s, the researchers reduced PDE4B activity in mice with the disease. The result: fewer memory problems, healthy levels of glucose metabolism, and less inflammation in the brain.
- “Reducing PDE4B activity could protect against cognitive impairment not only in Alzheimer’s disease, but also in other forms of dementia, such as Huntington’s disease,” according to the team of researchers.
A future treatment for Alzheimer’s disease? At least that is the hope raised by a recent study carried out on rodents, published in the journal Neuropsychopharmacology. While the number of people diagnosed with it should double by 2050a team of scientists has uncovered a new potential target for treating neurodegenerative pathology: the PDE4B gene.
Alzheimer’s: fewer symptoms in mice with an inhibited PDE4B gene
The PDE4B enzyme, encoded in humans by the eponymous gene, participates in the regulation of a whole range of cellular processes linked, for example, to hormones or neurotransmitters. Building on previous work that identified the PDE4B gene as a risk factor for Alzheimer’s, researchers at the Universities of Leeds and Lancaster in the United Kingdom wanted to know whether inhibiting PDE4B activity was likely to protect against the disease and, ultimately, be the basis of a new treatment. With this in mind, they genetically reduced (by just 27%) PDE4B activity in mouse models that had amyloid plaques in the brain, a key pathological hallmark of Alzheimer’s disease.
As a result, by confronting them with maze tests, the researchers observed “memory deficits” in rodents suffering from Alzheimer’s – unsurprisingly – but not in sick rodents whose PDE4B activity had been inhibited, we can read in a communicated. Using functional brain imaging, the team also observed that the metabolism of glucose, the main source of energy in the brain, was “altered” in Alzheimer’s diseased mice (like that observed in patients with the disease), but that those with reduced PDE4B activity showed “healthy levels of glucose metabolism in the brain”.
A protective effect on memory in mice with Alzheimer’s disease
To better understand the mechanisms at work, the scientists then examined the expression levels of genes and proteins in the brain. Same difference: if the inflammation was “increased” in the brains of mice suffering from Alzheimer’s (as is the case in humans), it was “weaker” in mice with the modified PDE4B gene.
“Although these rodents showed no decrease in the number of amyloid plaques in the brain, it had a profound protective effect on memory and glucose metabolism in the diseased mice. This suggests that it could protect against cognitive impairment. not only Alzheimer’s disease, but also other forms of dementia, such as Huntington’s disease. say the authors of the study. And to conclude: “These results offer real hope for the development of new treatments.”
