A recent study by researchers from the University of Gothenburg and elsewhere raises important questions about the accuracy of a blood test for Alzheimer’s disease (AD) in patients treated with the heart failure drug Entresto (sacubitril/valsartan).
Published in JAMA Neurology, the study’s findings indicate that Entresto significantly alters plasma Aβ ratios, potentially leading to misdiagnosis of AD.
Alzheimer’s disease is characterized by the accumulation of β-amyloid (Aβ) plaques in the brain. Entresto, primarily used for heart failure, combines a neprilysin inhibitor and an angiotensin receptor blocker.
Neprilysin is crucial for degrading Aβ in the brain, and initially, some concerns inhibiting it might increase AD risk.
However, the PERSPECTIVE trial showed that long-term neprilysin inhibition did not increase Aβ accumulation or cognitive decline, offering reassurance.
The plasma Aβ ratio test has emerged as a less invasive alternative to cerebrospinal fluid (CSF) and PET methods for detecting brain amyloidosis.
While it shows promise in research settings, its clinical robustness is debated due to the minor “fold change” it demonstrates in AD patients compared to healthy individuals. This small-fold change, reflecting a 10–12% reduction in AD, questions its suitability for clinical use.
The study assessed the impact of 52 weeks of Entresto vs. valsartan alone on AD blood biomarkers in 92 cardiac failure patients.
The results were striking: treatment with Entresto led to a marked increase in both plasma Aβ42 and Aβ40, with a more pronounced increase in Aβ40.
This resulted in a 32-34% reduction in the plasma Aβ ratio, which could falsely classify patients as Aβ plaque-positive, suggesting a misdiagnosis of Alzheimer’s disease.
This effect was observed in all patients treated with Entresto, with no changes noted in other AD blood biomarkers like pTau217, pTau181, GFAP, or NFL.
Given the prevalence of heart failure and Alzheimer’s in the US, with a significant overlap in patient populations, these findings are crucial.
Approximately 40% of heart failure patients also exhibit cognitive impairment, making them potential candidates for the Aβ blood test.
The study calls for caution in interpreting plasma Aβ42/Aβ40 test results in patients receiving Entresto, as it could lead to misclassification of their cognitive status.
Furthermore, it suggests the need to re-evaluate previous research on plasma Aβ tests to adjust for potential false positives due to Entresto treatment.
From a clinical and ethical standpoint, the researchers recommend contacting patients who underwent the plasma Aβ test to ascertain if they were on Entresto at the time, which might have led to false positive results.
This study highlights a critical interaction between a common heart failure treatment and Alzheimer’s diagnostics, urging a careful approach in diagnosing this complex neurological condition.
If you care about heart disease, please read studies that herbal supplements could harm your heart rhythm, and how eating eggs can help reduce heart disease risk.
For more information about heart health, please see recent studies that apple juice could benefit your heart health, and results showing yogurt may help lower the death risks in heart disease.
The research findings can be found in JAMA Neurology.
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