Early warning: Even in middle age, a blood test can detect early molecular signs of Alzheimer’s disease – long before dementia symptoms become noticeable, as a study has now confirmed. She also reveals: Even at this point, those affected show subtle losses in some cognitive performance. Their mental abilities also decline more quickly than their peers without positive biomarkers. An early blood test could therefore help to take countermeasures in good time, the doctors explain in “The Lancet”.
Alzheimer’s dementia develops gradually: long before the first symptoms become noticeable, neurodegenerative degradation begins in the brain, initiated by the accumulation of misfolded beta-amyloid and tau proteins. Because there is no cure and the loss of brain matter cannot be reversed, it is important to detect the onset of Alzheimer’s disease as early as possible. Only then can medication, but also adjustments to lifestyle and diet, at least slow down the progression of dementia.
Newly developed blood tests offer an opportunity to detect Alzheimer’s disease as early as possible. These detect misfolded beta-amyloid or tau proteins in the blood or molecular relics of dead brain cells. “So far, research on such tests has mostly focused on test subjects of older age,” explain Xiaqing Jiang from the University of California in San Francisco and her colleagues.
Biomarkers reveal Alzheimer’s long before noticeable symptoms appear
“We therefore wanted to know: Can the neuropathology of Alzheimer’s be detected by blood biomarkers as early as middle age? And is the presence of such signs linked to cognitive losses even at this age?” is how Jiang and her team describe the questions. To clarify this, they examined 1,350 healthy participants in a long-term US study between the ages of 53 and 69. Using blood tests, they determined the content of misfolded beta-amyloid and tau proteins in their blood plasma every five years, and they also tested cognitive performance using standardized tests.
The analyzes showed that the blood tests found results in around six percent of the test subjects. They detected strikingly increased levels of misfolded amyloid or tau proteins. This confirms that the biomarkers for Alzheimer’s dementia can be detected before retirement age. “The neuropathology of Alzheimer’s is therefore rare in midlife, but is already detectable,” explain the researchers.
Mental deficits already in middle age
More importantly, the cognitive tests revealed that these early molecular signs are linked to subtle mental declines in middle age. Although those affected still appear healthy and their memory still functions without problems, they perform significantly weaker in two core areas of cognitive performance than people without elevated Alzheimer’s biomarkers in their blood.
“Individuals with positive blood markers for Alzheimer’s showed poorer performance on tests of processing speed and executive functions,” report Jiang and her colleagues. In concrete terms, this means: On the one hand, those affected react less quickly to changing situations or information – for example, to unexpected turns in conversations or a changing traffic light. On the other hand, the first deficits become apparent when it comes to planning and organizing actions. The ability to stay on task and concentrate on a task also suffers when executive functions are impaired.
The follow-up tests after five years also showed that verbal memory declined two and a half to four times faster in people with positive Alzheimer’s biomarkers than in study participants who tested negative. Their brain’s processing speed deteriorated three to four times faster than controls.
Chance for early countermeasures
“Our study is one of the first to examine the association of early molecular signs of Alzheimer’s with mental performance in middle age,” the team writes. “We were able to show that neuropathological biomarkers in blood plasma are associated with poorer mental performance in several areas even in middle age.” At the same time, the result confirms that Alzheimer’s disease begins decades before noticeable clinical symptoms appear.
According to the researchers, such blood tests offer the opportunity to detect Alzheimer’s early and counteract mental decline at this early stage. So far, blood tests for Alzheimer’s disease have only been approved in the USA for patients with already measurable Alzheimer’s symptoms. However, the current study suggests that such tests can also be useful in supposedly healthy, symptom-free people – for example, in those who have genetic risk factors for Alzheimer’s.
“If we detect dementia early, affected patients could specifically change the risk factors that can be influenced,” explains senior author Kristine Yaffe from the University of California in San Francisco. Such risk factors include smoking, obesity, lack of exercise and too little mental stimulation, but also hearing loss, depression or cardiovascular diseases. According to Yaffe, around 40 percent of all Alzheimer’s cases could be delayed or prevented by specifically changing or treating these factors.
Source: Xiaqing Jiang (University of California, San Francisco) et al., The Lancet, 2026; doi: 10.1016.S0140-6736(26)00515-5