Lifelong choline supplementation ameliorates Alzheimer's disease pathology and associated cognitive deficits by attenuating microglia activation
Velazquez R, Ferreira E, Knowles S, Fux C, Rodin A, Winslow W, Oddo S (2019) Aging Cell. 2019 Sep: e13037. doi: 10.1111/acel.13037. [Epub ahead of print]
Abstract:
Currently, there are no effective therapies to ameliorate the pathological progression of Alzheimer's disease (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 choline supplementation 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.
Lifelong choline supplementation 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 lifelong choline supplementation produces profound benefits and suggest that simply modifying diet throughout life may reduce AD pathology.
FAB RESEARCH COMMENT:
This new animal study adds to the already substantial evidence that higher dietary choline intakes throughout life can protect against the development of dementia.It also shows that prevention of neuroinflammation is among the many mechanisms by which choline can protect the brain from the degenerative processes underlying age-related cognitive decline and dementia - as well as many other neurological and psychiatric disorders.
Choline is seriously lacking from most modern, western-type diets - and is not even currently included in most multivitamin supplements. This study powerfully reinforces the existing evidence that this widepsread dietary deficiency of choline is likely to be compromising brain function and cognition, as well as general health, at the population level.
See the associated news article and FAB comment for more information and details on this study, and on the importance of choline more generally for healthy brain development and function, as well as the best dietary sources:
And for more information on choline, see:
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