The high prevalence of Alzheimer’s disease in Down syndrome is due to the triplication of chromosome 21. This chromosome contains one of the genes in charge of regulating the synthesis of amyloid beta, a short chain of amino acids that can build up in the brain and interfere with brain function, resulting in cognitive impairments found in Alzheimer’s disease.
Being overweight or obese in middle age increases the risk of acquiring Alzheimer’s disease in persons who do not have Down syndrome. Fleming’s first curiosity was to investigate this link among people with Down syndrome. However, the results were unexpected.
“We were intrigued because when we looked at the data and the time course of when weight was changing, we saw a stronger story of unintentional weight loss being linked to early Alzheimer’s disease pathology in the brain,” says Sigan Hartley, a UW-Madison professor of human development and family studies and senior author of the new study.
The study examined data from 261 persons with Down syndrome aged 25 to 65 who were weighted at the start and again about 18 months later. They also took a battery of cognitive tests and had a brain scan to detect levels of amyloid beta and tau, proteins linked to Alzheimer’s disease.
Unintentional Weight Loss Linked with Amyloid Development in the Brain
People with Down syndrome in the study began losing weight unintentionally in their mid-30s, at the same time that amyloid development began. Furthermore, the patients with Down syndrome who lost the most weight had the highest accumulation of these proteins.
“The finding that unintentional weight loss appears to coincide in time with the accumulation of these proteins could signal that these processes are related or share causal pathways. This is something that we will be exploring next,” Hartley says.
The end outcome is what Hartley refers to as the weight dilemma.
“In midlife, having a higher BMI may put you at risk for Alzheimer’s disease. But Alzheimer’s disease pathology may be connected to weight loss. So, both could be true,” Hartley says.
The scientific explanations for this link between unintended weight loss and Alzheimer’s disease pathology are unknown to the scientists. According to one theory, amyloid buildup causes a shift in brain metabolism and hormone balance, resulting in fat and muscle loss.
Fleming’s future research will focus on how unintended weight loss occurs, as well as dissecting the weight paradox by examining midlife BMI and the trajectory of inadvertent weight loss across different time points in people with Down syndrome.
“We don’t have many good clinical signs that somebody could be nearing that cusp of cognitive decline in Alzheimer’s disease,” Hartley says. “Our results are exciting because they suggest that there may be some non-cognitive signs – including unintentional weight loss – that could help us predict who might be about to develop dementia earlier or later.”
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