Results challenge the view that Alzheimer’s is ‘intrinsically irreversible,’ the study states.
Scientists have reversed Alzheimer’s disease in mice, potentially showing a pathway to treat the illness among humans, according to a Dec. 22 peer-reviewed study published in the Cell Reports Medicine journal.
Alzheimer’s is traditionally considered irreversible. In the study, researchers treated two groups of mice with P7C3-A20, a pharmacologic agent. One group carried human mutations related to amyloid processing, while the other carried a tau protein mutation. Both amyloid and tau pathologies are two major early events of Alzheimer’s.
Researchers say that as mice develop brain pathologies resembling Alzheimer’s, they are ideal subjects to test how P7C3-A20 affects Alzheimer’s in humans.
Among the amyloid mice, treatment with P7C3-A20 was found to have resulted in restoring the proper balance of Nicotinamide adenine dinucleotide (NAD+), which is a cellular energy molecule and a major driver of Alzheimer’s disease. As people age, NAD+ levels decline in their bodies, including the brain. Without proper NAD+ balance, the cells are unable to execute critical processes necessary for proper functioning.
The treatment was found to have reversed blood-brain barrier deterioration, DNA damage, oxidative stress, and neuroinflammation, researchers wrote. The blood-brain barrier maintains nutrient and hormone levels in the brain while protecting the organ from toxins and pathogens.
The treatment enhanced synaptic plasticity and hippocampal neurogenesis, a process in which new functional neurons are generated.
These changes resulted in “full cognitive recovery and reduction of plasma levels” of p-tau217 among the amyloid mice, researchers said. P-tau217 is the clinical biomarker of Alzheimer’s that helps predict cognitive decline.
In fact, when P7C3-A20 was initiated for 6-month-old mice as they manifested advanced Alzheimer’s pathology and cognitive deficits, the treatment “comprehensively restored brain health and function by 12 months,” researchers wrote in the study.
P7C3-A20 reversed advanced Alzheimer’s in mice with tau mutation and was found to help protect the human brain microvascular endothelial cells (BMEC) from oxidative stress. BMEC is the major component of the blood-brain barrier.
“Our results challenge the long-held view that [Alzheimer’s disease] is intrinsically irreversible,” the researchers wrote.
They said that restoring the proper balance of NAD+ levels may be “a potentially transformative therapeutic approach.”
Multiple study authors declared competing interests for holding patents related to subjects covered under the study.
