Good news! This could be a major breakthrough!
"... Through studying diverse preclinical mouse models and human AD brains, the team showed that the brain's failure to maintain normal levels of a central cellular energy molecule, NAD+, is a major driver of AD, and that maintaining proper NAD+ balance can prevent and even reverse the disease.
NAD+ levels decline naturally across the body, including the brain, as people age. Without proper NAD+ balance, cells eventually become unable to execute critical processes required for proper functioning and survival.
In this study, the team showed that the decline in NAD+ is even more severe in the brains of people with AD, and that this also occurs in mouse models of the disease. ...
the research team tested whether preventing the loss of brain NAD+ balance before disease onset, or restoring brain NAD+ balance after significant disease progression, could prevent or reverse AD, respectively.
The study was based on their previous work, published in Proceedings of the National Academy of Sciences, showing that restoring the brain's NAD+ balance achieved pathological and functional recovery after severe, long-lasting traumatic brain injury. They restored NAD+ balance by administering a now well-characterized pharmacological agent known as P7C3-A20, developed in the Pieper lab.
Remarkably, not only did preserving NAD+ balance protect mice from developing AD, but delayed treatment in mice with advanced disease also enabled the brain to fix the major pathological events caused by the genetic mutations. Moreover, both lines of mice fully recovered cognitive function.
This was accompanied by normalized blood levels of phosphorylated tau 217, a recently approved clinical biomarker of AD in people ..."
From the highlights and abstract:
"Highlights
• Severity of Alzheimer’s disease (AD) correlates with NAD+ homeostasis dysregulation
• Preserving brain NAD+ homeostasis prevents AD in mice
• Restoring brain NAD+ homeostasis reverses advanced AD in mice
• Multiomics across human and mouse AD brain identifies nodes for human AD reversal
Summary
Alzheimer’s disease (AD) is traditionally considered irreversible.
Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217.
P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress.
In humans and mice, pathology severity correlates with disruption of brain NAD+ homeostasis, and the brains of nondemented people with Alzheimer’s neuropathology exhibit gene expression patterns suggestive of preserved NAD+ homeostasis.
Forty-six proteins aberrantly expressed in advanced 5xFAD mouse brain and normalized by P7C3-A20 show similar alterations in human AD brain, revealing targets with potential for optimizing translation to patient care."
Alzheimer's disease can be reversed in animal models to achieve full neurological recovery
Graphical abstract
Figure 1 P7C3-A20 restores brain NAD+ homeostasis, cognitive function, and synaptic plasticity in aged symptomatic 5xFAD mice
