Currently, there are no effective therapies to ameliorate the pathological progression of Alzheimer'sdisease (AD). Evidence suggests that environmental factors may contribute to AD. Notably, dietary nutrients are suggested to play a key role in mediating mechanisms associated with brain function.
Choline is a B-like vitamin nutrient found in common foods that is important in various cell functions. It serves as a methyl donor and as a precursor for production of cell membranes. Choline is also the precursor for acetylcholine, a neurotransmitter which activates the alpha7 nicotinic acetylcholine receptor (α7nAchR), and also acts as an agonist for the Sigma-1 R (σ1R). These receptors regulate CNS immune response, and their dysregulation contributes to AD pathogenesis.
Here, we tested whether dietary cholinesupplementation throughout life reduces AD-like pathology and rescues memory deficits in the APP/PS1 mouse model of AD. We exposed female APP/PS1 and NonTg mice to either a control choline (1.1 g/kg choline chloride) or a choline-supplemented diet (5.0 g/kg choline chloride) from 2.5 to 10 months of age. Mice were tested in the Morris water maze to assess spatial memory followed by neuropathological evaluation. Lifelongcholinesupplementation significantly reduced amyloid-β plaque load and improved spatial memory in APP/PS1 mice. Mechanistically, these changes were linked to a decrease of the amyloidogenic processing of APP, reductions in disease-associated microglial activation, and a downregulation of the α7nAch and σ1 receptors.
Our results demonstrate that lifelongcholinesupplementation produces profound benefits and suggest that simply modifying diet throughout life may reduce AD pathology.
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