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MONDAY, July 29, 2024 -- A new test gauging levels of key proteins in the blood was far more accurate than doctor assessments in spotting Alzheimer's disease in people with early-stage illness. The test, called APS2 (the amyloid probability score 2), was 91% accurate in diagnosing Alzheimer's in people with mild cognitive decline or early dementia, compared to the 61% success rate of primary care doctors who examined the same patients. The test isn't yet approved for routine use. But Dr Teresa D'Amato , director of geriatric emergency medicine at Northwell Health in Forest Hills, NY, called the new data "very exciting." "This blood test would be great as a first round of diagnostic testing because it it looks like it's pretty accurate," said D'Amato, who wasn't involved in the new study. The findings were published July 28 in the Journal of the American Medical Association . They were published simultaneously at the Alzheimer’s Association International Conference in Philapdelphia. An accurate, easily administered blood test for Alzheimer's could be a game-changer, according to a team of dementia experts who wrote an editorial accompanying the research. "Diagnosing Alzheimer's is challenging, especially in primary care. Having a reliable blood test is essential to help primary care physicians make an early and accurate diagnosis," the editorialists said. They included Dr. Stephen Salloway , of Brown University, Dr. Christopher Rowe , of the University of Melbourne, Australia, and Dr. Jeffrey Burns , of the University of Kansas Medical Center. The new test was developed by a team led by Dr. Sebastian Palmquist . of Skane University Hospital and Lund University in Malmo, Sweden. The recent advent of drugs that slow Alzheimer's in its earliest stages have made the search for an easier, more accurate diagnostic test more urgent. "It becomes really important to diagnose Alzheimer’s very early on to make these folks eligible for possible treatment," D'Amato said. The new test relies on relative blood levels of two types of proteins whose buildup in the brain has long been a hallmark of Alzheimer's: Tau "tangles" and amyloid "plaques." In the study, 1,213 patients who were experiencing "cognitive symptoms" were evaluated by either a standard primary care physician exam or by the use of the APS2 test. The patients averaged about 74 years of age. Overall, 23% had "subjective cognitive decline," 44% had "mild cognitive impairment" and 33% had already been diagnosed with dementia. Patients were assessed by primary care physicians who relied on standard, internationally recognized criteria as well as CT scans and cognitive tests. Patients also got the APS2 blood test. Results from each of those screening methods were compared to "gold standard" tests for Alzheimer's (cerebrospinal fluid tests and PET scans looking for amyloid and tau in the brain). According to Palmquist's group, the ASPS2 ended up being 91% accurate in spotting Alzheimer's disease in patients, compared to the 61% accuracy of the primary care doctors. The blood test even beat dementia specialists: They were 73% correct in their diagnoses compared to the 91% accuracy of the blood screen. Of the two proteins being measured by the test, tau seemed by far to be the most important. In fact , looking at tau protein measurements alone produced an equally high accuracy (90%) in diagnosing Alzheimer's disease, the team found. The three editorial authors stressed that questions remained, however. Would the test be economical enough for use in doctors' offices? Will it gain FDA approval for use? And will the ASPS2 test be outshone by other Alzheimer's blood screens also in development? Still, "this study makes the case convincingly that highly sensitive blood measures of Alzheimer disease can be integrated into the clinical decision-making process, including in the primary care setting," they wrote. "The way that I think we envision it being used is that someone would come in [to their doctor] with cognitive decline," D'Amato explained. "A physician would do all the blood work that you would normally do to rule out all the other reasons for cognitive decline and, in addition, send these new blood tests looking for the amyloid and the tau and the blood. And that could be a screening exam. " "I think if it's used correctly it could be an exciting adjunct to diagnosing Alzheimer's sooner than later," she said. However, Palmquist's team stressed that a blood test will never be the only means of diagnosing Alzheimer's early in its development. That's because Alzheimer's can take years to develop in the brain and symptoms that resemble early Alzheimer's can also be caused by other conditions. "Incorrect interpretation of a positive Alzheimer disease biomarker [test] could thus lead to under-diagnosis of relatively common non-Alzheimer disease conditions," the study authors explained. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

The original PrecivityAD blood test used mass spectrometry to measure amyloid beta 42 and 40. The expanded version of C2N’s blood test, meanwhile, adds another ratio to the mix, this one comparing the presence of phosphorylated and non-phosphorylated tau217. The company has said that the addition improves the test’s ability to determine whether a patient is positive or negative for brain amyloid plaques. Late last year, C2N Diagnostics unveiled the second generation of its liquid biopsy technology to screen for Alzheimer’s disease, and now, it’s putting that blood test to the test. The company presented a pair of studies of the PrecivityAD2 test at the annual AD/PD conference—which focuses on new findings surrounding Alzheimer’s and Parkinson’s diseases and concluded earlier this month—both highlighting the test’s ability to measure amyloid plaques in the brain, a telltale sign of the development of Alzheimer’s. The original PrecivityAD test used mass spectrometry to measure amyloid beta 42 and 40 and to look for apolipoprotein E (ApoE), another potential indicator of Alzheimer’s. C2N’s algorithms then used the patient’s resulting Aβ42/40 ratio and ApoE genotype to calculate their amyloid probability score, or APS, suggesting the likelihood that they had Alzheimer’s or were at risk of developing the disease—though follow-up testing was required to make a definitive diagnosis. The expanded version of C2N’s blood test, meanwhile, combines the Aβ42/40 ratio with another ratio, this one comparing the presence of phosphorylated and non-phosphorylated tau217. The company has said that adding tau into the mix improves the test’s ability to determine whether a patient is positive or negative for brain amyloid plaques, results that are expressed as APS2. Though the first PrecivityAD test is already available via prescription in almost every U.S. state, PrecivityAD2 is still marked for research use only. The first of the two studies, according to a release from C2N earlier this month, was conducted on just over 300 Swedish patients who were showing symptoms of cognitive impairment, each of whom was given the PrecivityAD2 test alongside either a cerebrospinal fluid analysis or an amyloid PET scan, two of the current standards for Alzheimer’s screening. Not only did the blood tests’ APS2 results achieve an area under the curve of 94% when compared to the results of the other tests, but they also helped improve doctors’ diagnoses: According to C2N, when the APS2 results weren’t factored into the diagnostic process, primary care doctors accurately diagnosed symptomatic cases of Alzheimer’s only 60% of the time, resulting in an overdiagnosis of 23% of patients and an underdiagnosis of 17%. “The primary care physicians’ diagnosis certainty with standard of care only was low, which highlights that they are completely aware that currently available diagnostic tools in primary care are not adequate. The results we’ve seen so far indicate that this can radically change with a blood test for AD,” Sebastian Palmqvist, M.D., Ph.D., a neurologist who helped lead the study said in the release, adding, “The PrecivityAD2 data represent the highest correlation data I’ve seen for a blood test against corresponding CSF biomarkers.” The second study put the PrecivityAD2 test head-to-head with other blood biomarker tests for Alzheimer’s—but focused on individuals showing no signs of cognitive impairment. The main component of the study used several of these blood tests to analyze Alzheimer’s risk in 281 cognitively unimpaired people. PrecivityAD2 scored the highest diagnostic accuracy of them all, per C2N, with an area under the curve of about 96% in detecting brain amyloid plaques. The researchers then looked even further into the use of blood-based biomarkers to predict cognitive decline over time, by studying nearly 300 patients over an average of about eight years. They found that the p-tau217 ratio included in the PrecivityAD2 test served as the best predictor of cognitive decline, according to the test’s maker.