Protein clue may explain why women with Alzheimer’s tend to decline more quickly than men

Women had higher rates of connectivity between key regions of the brain which may act as 'hubs' and allow toxic proteins that kill brain cells to spread

Women with dementia outnumber men with the disease "two to one" but female brain remains poorly studied (Shutterstock)

Women suffering from Alzheimer’s disease may experience a more rapid decline than men with the same condition because their brains have a higher number of connections, making it easier for toxic protein molecules to spread, a study has suggested.

Researchers studying differences in the onset of Alzheimer’s in men and women believe this could explain how clumps of abnormal tau protein molecules, which characterise the disease, disperse more rapidly in female brains.

Women are twice as likely to develop Alzheimer's but this had been believed to be a consequence of them living longer. The latest findings, led by Vanderbilt University Medical Centre, in Tennessee, suggest there may be a more fundamental biological reason.

The team compared brain scans from healthy volunteers, 123 men and 178 women, with 101 men and 60 women with mild cognitive impairment that indicates they are at higher risk of developing Alzheimer’s.

They found that women with cognitive impairment had nearly twice the density of tau proteins across the brain than cognitively impaired men.

In cognitively normal adults there was little difference in the density of tau proteins, which are believed to be waste products of brain cellular activity that build up to toxic levels following the onset of Alzheimer’s.

Scans of healthy women’s brains did reveal that they had several key brain regions – such as the parahippocampus, superior parietal, insular, superior temporal – which served as “hubs” to link different parts of the brain where tau had built up.

They speculate this connectivity could “accelerate brain-wide tau spread in women” and explain their faster decline.

“The differences that we observed indicate the strong possibility that there are sex differences in the structural and functional connections in the brain, which may contribute to women’s increased risk for Alzheimer’s,” said Dr Sepideh Shokouhi, who led the research.

“This study has implications for the possibility of creating sex-specific risk-reduction strategies and preventive interventions.”

The Vanderbilt study is one of several pieces of preliminary research, as yet unpublished in a peer reviewed journal, looking at sex differences in dementia. They are being presented at the Alzheimer’s Association International Conference in Los Angeles on Tuesday.

A separate study, by the University of Miami, found a number of genes that appear to be linked with a higher risk of the disease, but only in either men or women. This suggests risk predictions – and potential future treatments – may have to be sex-specific.

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“The facts speak for themselves – women living with dementia outnumber men two to one across the world,” Fiona Carragher, chief policy and research officer at the UK’s Alzheimer’s Society, said.

“Dementia also affects women differently, with symptoms like delusions, depression and reclusiveness experienced more widely in women than men.

She said the Vanderbilt findings add “flesh to the bones” of our knowledge by suggesting tau spreads more quickly in women’s brains and this could be causing a faster rate of brain cell die off.

“Women’s brain health is an under-studied topic, and, historically, the lion’s share of dementia research has focused on men.”