Home Mind & Brain Ketogenic Diet Shows Promise in Alzheimer’s Disease Treatment Through Synaptic Plasticity Enhancement

Ketogenic Diet Shows Promise in Alzheimer’s Disease Treatment Through Synaptic Plasticity Enhancement

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Researchers have demonstrated the potential of the ketogenic diet (KD) for treating Alzheimer’s disease (AD) by enhancing synaptic plasticity without altering amyloid beta (Aβ) levels. This discovery offers a new therapeutic avenue that could ameliorate the memory and cognitive deficits associated with AD.

Alzheimer’s disease, a progressive neurodegenerative disorder, is characterised by the accumulation of Aβ peptides, which form plaques, leading to synaptic dysfunction and cognitive decline. Traditional therapeutic approaches have primarily focused on targeting Aβ accumulation. But this study shifts the focus towards enhancing synaptic function as a viable strategy for alleviating symptoms.

Professor Gino A. Cortopassi from the University of California, Davis, added insight into the broader implications of ketogenic diets: “Our group had shown earlier that the ketogenic diet extends longevity ~13% in mice and also improves cognitive and physical functions in later age. This means the ketogenic diet increased both lifespan and health span in mice.”

The findings were published in the journal Communications Biology.

The research was conducted using the APP/PS1 mouse model, an established experimental system for studying Alzheimer’s disease. The study focused on the impact of a seven-month-long ketogenic diet regimen, starting in the sixth month of the mice’s lifespan. Ketogenic diets are high in fat and low in carbohydrates, leading to increased levels of ketone bodies like beta-hydroxybutyrate (BHB).

BHB, identified as the “active principle” of the KD, plays a crucial role in this process. Unlike many treatments that attempt to reduce Aβ levels, KD works by increasing BHB levels, which in turn enhances synaptic plasticity – a key component of memory and learning. Synaptic plasticity refers to the ability of synapses to strengthen or weaken over time, which is essential for learning and memory.

Professor Cortopassi elaborated on a key finding related to BHB: “A very significant key finding needs a bit of explanation. We (and others) suggest that beta-hydroxybutyrate (BHB) may drive the keto diet’s key benefits—in mice on keto, the levels of BHB rise 2–3 fold vs the standard carbohydrate-rich diet. We tested the effect of soaking the brains for one hour with BHB, and this significantly rescued their LTP memory trace, just as did seven months of the keto diet. This strongly supports the idea that, in the keto diet, increased BHB levels reduce age-related memory loss. The results support the idea that BHB supplements may be helpful.”

Results from the study showed that mice on the ketogenic diet maintained normal levels of long-term potentiation (LTP), an important physiological marker of synaptic plasticity. LTP in the hippocampus of APP/PS1 mice on a standard diet was deficient, aligning with the characteristic memory deficits observed in Alzheimer’s disease. Notably, the ketogenic diet did not alter Aβ levels in the hippocampus, suggesting that its beneficial effects are mediated through other mechanisms, primarily synaptic enhancement.

Further biochemical analysis supported these findings, showing significant increases in the levels of synaptic plasticity-related enzymes such as phospho-ERK and phospho-CREB in the hippocampus of KD-fed mice. This indicates that the ketogenic diet activates key signalling pathways involved in synaptic strength and health.

Moreover, the study highlights the gender-specific effects of the ketogenic diet, where increased levels of brain-derived neurotrophic factor (BDNF) were observed only in female mice. BDNF is a protein that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses.

Professor Cortopassi shared their future plans: “We are in our last year of funding and now propose to test the keto diet’s safety, feasibility and efficacy in a human clinical study.”

The implications of these findings are profound. By preserving synaptic function through dietary means, there is potential to delay or mitigate the cognitive decline associated with Alzheimer’s disease, offering a non-invasive and accessible treatment option.

This study opens up new possibilities for dietary interventions in the management of Alzheimer’s disease, emphasising the need for further research to explore the full therapeutic potential of ketogenic diets in human patients.

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