New Alzheimer's Blood Test 94% Accurate
MEDSCAPE Megan Brooks August 02, 2019
A new blood test to detect brain changes emblematic of early Alzheimer's disease (AD) has moved one step closer to reality and could be a "game changer" for the field. Researchers found that measuring the ratio of β-amyloid (Aβ) 42 and Aβ40 in blood using a high-precision assay is 94% accurate in diagnosing brain amyloidosis, using amyloid PET or CSF phosphorylated (p-tau) 181/Aβ42 as reference standards.
"Right now we screen people for clinical trials with brain scans, which is time-consuming and expensive, and enrolling participants takes years," senior investigator Randall J. Bateman, MD, professor of neurology, Washington University School of Medicine in St. Louis, said in a statement.
"But with a blood test, we could potentially screen thousands of people a month. That means we can more efficiently enroll participants in clinical trials, which will help us find treatments faster, and could have an enormous impact on the cost of the disease as well as the human suffering that goes with it," he added.
The study was published online August 1 in Neurology.
Easy Screening Tool
Using an immunoprecipitation and liquid chromatography–mass spectrometry assay, the researchers measured Aβ42/Aβ40 in plasma and CSF samples from 158 older, mostly cognitively normal individuals (94% with Clinical Dementia Rate [CDR] = 0) that were collected within 18 months of an amyloid PET scan.
Plasma Aβ42/Aβ40 correlated highly with amyloid PET status (receiver operating characteristic area under the curve [AUC], 0.88; 95% confidence interval [CI], 0.82 - 0.93) and CSF p-tau181/Aβ42 (AUC, 0.85; 95% CI, 0.79 - 0.92), the researchers report.
The combination of plasma Aβ42/Aβ40, age, and apolipoprotein (APOE) ε4 status had "very high" correlation with amyloid PET (AUC, 0.94; 95% CI, 0.90 - 0.97), "suggesting that plasma Aβ42/Aβ40 may be used as a screening tool for those at risk of AD dementia," the researchers write.
In addition, individuals with a positive plasma Aβ42/Aβ40 but negative amyloid PET scan have a 15-fold higher risk of converting to amyloid PET-positive (P = .01).
"The sensitivity of the plasma Aβ42/Aβ40 assay to amyloid PET-negative individuals who convert to amyloid PET-positive suggests that plasma Aβ42/Aβ40 becomes positive earlier than the established amyloid PET threshold used for this study," Bateman and colleagues note in their report.
"Therefore, a positive plasma Aβ42/Aβ40 with a negative amyloid PET scan may represent early amyloidosis rather than a false-positive result in some individuals," they add.
As reported by Medscape Medical News, the study builds on earlier work by the same researchers.
The most immediate use of the plasma Aβ42/Aβ40 assay is screening for brain amyloidosis in potential participants for AD drug trials, the investigators note.
The plasma Aβ42/Aβ40 screen would significantly reduce the number of confirmatory tests, such as amyloid PET or CSF biomarkers, required to select individuals with brain amyloidosis, especially in the case of prevention trials, which recruit cognitively normal individuals who have a relatively low rate of brain amyloidosis.
Researchers estimate that for a prevention trial similar to the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study, prescreening with plasma Aβ42/Aβ40 would reduce the number of amyloid PET scans required by 62%, "resulting in substantially reduced time and costs for recruitment."
A "Game Changer"
These findings could be a "game changer" for the AD research field, write Barbara Bendlin, PhD, of the Wisconsin Alzheimer's Disease Research Center in Madison, and Henrik Zetterberg, MD, PhD, of the UK Dementia Research Institute in London, in an editorial published with the study.
"The results are impressive," they add, in showing that a ratio of these two peptides is associated with amyloid PET as well as with CSF p-tau/Aβ42 ratio.
"Remarkably, in a small subset of individuals who were negative for amyloid on PET imaging at baseline, the plasma assay predicted future conversion to amyloid positivity on PET imaging," they point out.
"The results of this study resonate well with earlier studies and point toward the real possibility of using a plasma biomarker to screen for brain amyloidosis," they add.
However, in the context of clinical care, more work is needed, Bendlin and Zetterberg caution.
They note that participants in the study were largely cognitively unimpaired, which from the perspective of preclinical treatment initiation is desirable, but would limit generalizability to the typical clinic population.
Neurology. Published online August 1, 2019.