Protein plaques are believed to be a major cause of Alzheimer’s disease, which affects over half-a-million people in the UK alone, says James Witts. However, a new study out of Purdue University in the USA suggests that the main culprit may actually be a build-up of fat in the brain.
Could brain fat cause Alzheimer’s?
The research, featured in the journal Immunity, revealed that excess fat impaired the ability of the brain’s immune cells, known as microglia, to fight disease. As it stands, most Alzheimer’s drugs target the main suspects of the disease – namely the plaques of a misfolded protein called ‘amyloid beta’ and tangles of the protein ‘tau’ – but the revelation by a team led by lead author Gaurav Chopra could open the door to new therapies to target dementia and Alzheimer’s that focus on boosting the health of microglial function.
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“Directly targeting plaques or tangles will not solve the problem; we need to restore function of immune cells in the brain,” Chopra said. “We’re finding that reducing accumulation of fat in the diseased brain is the key, as accumulated fat makes it harder for the immune system to do its job and maintain balance.”
Microglial keeps the brain working in tip-top condition by clearing out debris, like amyloid beta and tau. Microglial absorb and break them down through a process called ‘phagocytes’. Chopra and his team directed their attention to fat-rich cells surrounding diseased areas of the brain, including the microglia.
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While it’s long been known that those with Alzheimer’s disease have high levels of lipid droplets, these were thought not to play a role in such neurogenerative diseases and dismissed as a by-product of the disease. However, the microglia cells close to the plaques featured such a high level of fat that they became overloaded and immobilised, the study found. “Because of these fatty deposits, microglial cells become dysfunctional – they stop clearing amyloid beta and stop doing their job,” Chopra explained.
By targeting these pathways, Chopra continued, it could be possible to restore the ability of immune cells like microglia to fight disease and keep the brain in balance. “What we’ve seen is that when we target the fat-making enzyme and either remove or degrade it, we restore the microglia’s ability to fight disease and maintain balance in the brain, which is what they’re meant to do.”
We watch these developments with interest, albeit further research is needed before this mechanism is proved and a subsequent drug passed for public use. However, there are non-pharmaceutical strategies to slow the progression and improve the symptoms of Alzheimer’s including outdoor exercise.
Exercise increases bloodflow and oxygen delivery to the brain. This supports the growth of new neurons in the hippocampus. This is responsible for memory, and it usually shrinks if you have Alzheimer’s disease. It also helps to regulate lipid metabolism, which has the potential to indirectly reduce stress on the microglia by limiting harmful lipid build-up.
Exercising outdoors cranks up the benefits as navigating varied terrain and environments supports spatial awareness and memory circuits, which are both affected by Alzheimer’s disease.
Regular physical activity, like a brisk walk and gardening, is also linked to a significantly lower chance of developing dementia – up to 35% according to a 2024 study in the British Journal of Sports Medicine.
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Main image: Alzheimer's disease affecting the hippocampus. Credit: Getty