It wasn't that long ago that the only way to test for Alzheimer's disease was to perform an autopsy on someone who had been suffering from dementia to look for the telltale tangles of tau and amyloid proteins in the brain. While these tangles are not necessarily the cause of Alzheimer's disease, they are certainly its major hallmark; their sticky, clumping action in the brain is at least partly responsible for the cognitive decline that all Alzhimer's patients experience.
Now, thanks to advances in medicine, doctors have the option of looking for these proteins using blood tests and, even more definitively, through the use of PET scans.
Scientists have also developed a protocol that looks for certain sugar molecules in the blood. When that information is combined with a memory test and genetic analysis, the data can be used to predict the onset of Alzheimer's with 80% accuracy up to 10 years in advance of its symptoms.
Still, pinpointing the exact progression of the disease using any of these methods has proven elusive – and it's a critical milestone to hit because many current and proposed treatments for Alzheimer's work better in the earlier stages of the disease.
Even though PET scans are the current gold standard of analyzing someone's degree of Alzheimer's, the scans themselves can be costly and not widely available except in population centers with advanced medical facilities.
It's in the blood
So researchers at Washington University in St. Louis (WashU) and Lund University (LU) in Sweden set out to find a better way.
Previously, the WashU researchers had linked the level of a protein known as MTBR-tau243 in cerebrospinal fluid as a valid proxy for levels of tau tangles in the brain. Getting this fluid through spinal taps, though, carries risk, is uncomfortable for patients and again, can be costly.
Now the WashU and Lund team has figured out a way to map blood levels of MTBR-tau243 to brain-based tau tangles and therefore use it to identify the stage of the disease's progression in any one patient.
The researchers did this by looking at a range of people with Alzheimer's, along with healthy people, and compared the levels of MTBR-tau243 in the blood with their brain scans. This allowed them to create a guide that matched blood levels to brain levels of the damaging substances.
They found that their method was 92% accurate at predicting tau tangles in the brain from the blood test. MTBR-tau243 was found to be significantly elevated in Alzheimer's patients with mild cognitive decline, while it was up to 200 times higher in those with full-blown dementia. The test was also able to sift those with Alzheimer's from those suffering from dementia from other causes, meaning that treatment options could be more precisely administered.
"We're about to enter the era of personalized medicine for Alzheimer's disease," said co-first author Kanta Horie from WashU Medicine. "For early stages with low tau tangles, anti-amyloid therapies could be more efficacious than in late stages. But after the onset of dementia with high tau tangles, anti-tau therapy or one of the many other experimental approaches may be more effective."
"Once we have a clinically available blood test for staging, plus treatments that work at different stages of the disease, doctors will be able to optimize their treatment plans for the specific needs of each patient," she added.
The researchers point out that the new blood test could eventually be combined with the blood test they've already licensed to C2N Diagnostics, a WashU spinout, that looks for another form of tau protein called p-tau217.
"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 Oskar Hansson, from LU. "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."
The team's new research has been published in the journal Nature Medicine.
Source: WashU Medicine
