Higher vitamin D in midlife linked to fewer tau tangles in Alzheimer's disease

Vitamin D in midlife and tau tangles

New research has associated vitamin D levels during midlife with the toxic tau protein tangles that build up in the brains of people with Alzheimer's disease.

An analysis of blood samples and brain scans from 793 adults found that people with more vitamin D in their system in middle age generally had fewer tau protein tangles years afterwards.

The result comes from an international research team. Although it does not establish a direct cause-and-effect relationship, it points to an association that warrants further investigation.

"These results suggests that higher vitamin D levels in midlife may offer protection against developing these tau deposits in the brain and that low vitamin D levels could potentially be a risk factor that could be modified and treated to reduce the risk of dementia," says neuroscientist Martin David Mulligan, from the University of Galway in Ireland.

"Of course, these results need to be further tested with additional studies."

How the researchers assessed vitamin D and Alzheimer's markers

As part of an initial assessment, the participants had their vitamin D levels measured once at age 39. Brain scans performed an average of 16 years later were used to evaluate tau and amyloid-beta levels, the latter being another protein strongly associated with Alzheimer's.

The research did not examine dementia diagnoses: none of the participants had Alzheimer's disease when their brain imaging was carried out. Instead, unusual tau and amyloid-beta behaviour served as an indicator of Alzheimer's-like brain changes that may have been beginning to develop.

Tau and amyloid-beta are not inherently harmful, as the brain requires both proteins to remain healthy. Damage linked to Alzheimer's starts when these proteins malfunction and obstruct neurons, causing brain cells to deteriorate and disrupting communication between them.

No association was identified between vitamin D and amyloid-beta. However, the analysis did reveal a relationship between vitamin D and tau, both across the brain as a whole and in several regions known to be affected during Alzheimer's earliest stages.

"To the best of our knowledge, there have been no previous studies evaluating an association between serum vitamin D and neuroimaging markers of preclinical dementia," write the researchers in their published paper.

"Supplementation with higher doses of vitamin D, and/or over longer periods of time in younger, cognitively healthy individuals may be beneficial, as the window of opportunity for disease modification is greater. However, this will require formal testing in clinical trials."

Vitamin D as a potentially modifiable dementia risk factor

Earlier research has connected vitamin D with a range of health benefits and with protection against dementia. This study now adds a link with a protein associated with Alzheimer's. It remains uncertain whether tau tangles are an underlying cause of the disease or simply one of its symptoms, but they are still among the earliest indications that something is wrong.

The researchers highlight previous studies showing that vitamin D can beneficially regulate the brain's immune system. Vitamin D deficiency has also been associated with abnormal tau protein behaviour in mouse brains.

Alzheimer's risk is influenced by many factors, ranging from harmful proteins to the genetics people are born with. It is a complicated picture, though scientists are progressively gaining a clearer understanding of its finer details.

The findings indicate that ensuring sufficient vitamin D could reduce some portion of this disease risk, making it perhaps worthwhile to spend more time in the sunshine or include more fish in the diet.

Nevertheless, vitamin D intake will need to be monitored more comprehensively across decades and connected with dementia diagnoses before any certainty is possible.

"These results are promising, as they suggest an association between higher vitamin D levels in early middle-age and lower tau burden on average 16 years later," says Mulligan.

"Midlife is a time where risk factor modification can have a greater impact."

The research has been published in Neurology Open Access.