While current blood tests for Alzheimer's help clinicians diagnose the condition, they do not indicate the degree of cognitive impairment that has occurred. As current treatments for Alzheimer's are most effective in the early stages of the condition, understanding how far the condition has progressed could help doctors determine which patients could benefit from which interventions and by how much.
In previous research, scientists found that levels of a protein called MTBR-tau243 in cerebrospinal fluid closely correlate with tau tangles in the brain, which correlate with the emergence and worsening of cognitive symptoms. In the current study, the same scientists extended their analysis to blood, which is easier to collect than cerebrospinal fluid.
For the study, they first developed an approach to measure levels of MTBR-tau243 in people's blood and to compare it to amounts of tau tangles in their brains. They piloted their technique on data from two cohorts, one including 108 people from the US, and one including a subset of 55 people from the BioFINDER-2 cohort in Sweden.
They then validated their approach on the remaining 739 people from the BIOFINDER-2 cohort. The cohorts included participants with levels of cognitive impairment ranging from cognitively unimpaired to mild cognitive impairment and Alzheimer's dementia.
Ultimately, the researchers found that blood MTBR-tau243 levels correlated with cerebrospinal fluid levels of MTBR-tau243 92% of the time. While blood levels of MTBR-tau243 among presymptomatic individuals were the same as those seen in healthy individuals, levels were significantly elevated among those in the cognitive impairment phase of Alzheimer's, and up to 200 times higher among those in the dementia stage.
The researchers further found that MTBR-tau243 levels were normal among people with cognitive symptoms related to conditions other than Alzheimer's. This suggests that tests assessing MTBR-tau243 levels could be used to distinguish Alzheimer's dementia from other kinds of dementia.
"I believe we will use blood-based p-tau217 to determine whether an individual has Alzheimer's disease, but MTBR-tau243 will be a highly valuable complement in both clinical settings and research trials," said co-senior author of the study, Oskar Hansson, MD, PhD, a professor of neurology at Lund University, in a press release.
"When both of these biomarkers are positive, the likelihood that Alzheimer's is the underlying cause of a person's cognitive symptoms increases significantly, compared to when only p-tau217 is abnormal. This distinction is crucial for selecting the most appropriate treatment for each patient," he added.
Sources: Science Daily, Nature Medicine
