Alzheimer’s Blood Marker Also Signals Heart & Kidney Disease, Study Finds
Alzheimer’s Blood Test Complicated by Similar Signal in Other Amyloid Diseases
A blood test designed to detect early signs of Alzheimer’s disease also registers a signal in patients with amyloid diseases affecting the heart and kidneys, according to a new study, potentially complicating its use as a standalone diagnostic tool.
Researchers analyzing blood samples from 280 older adults in Germany, Italy, and the Netherlands found elevated levels of phosphorylated tau (pTau) – a protein biomarker associated with Alzheimer’s – not only in those with the neurodegenerative disease, but also in individuals with systemic amyloidosis. The findings suggest the blood marker may be indicative of amyloid buildup throughout the body, rather than solely within the brain.
The study, led by Mathias Jucker at the German Center for Neurodegenerative Diseases (DZNE), focused on two specific systemic amyloid disorders: transthyretin amyloidosis and light-chain amyloidosis. Transthyretin amyloidosis involves misfolded proteins accumulating in the heart, causing stiffness and impaired blood flow. Light-chain amyloidosis, a different form of the disease, can damage the kidneys, leading to swelling, fatigue, and organ dysfunction.
For years, pTau has been a promising biomarker for Alzheimer’s disease, as it rises in blood tests even before the onset of noticeable memory loss. One major study demonstrated the test’s ability to differentiate Alzheimer’s from other brain disorders with approximately 90 percent accuracy. Though, the new research indicates that elevated pTau levels can also reflect protein damage outside the brain.
Both transthyretin and light-chain amyloidosis fall under the umbrella of systemic amyloidosis, where abnormal protein deposits accumulate in organs beyond the brain. A particularly insidious form, wild-type transthyretin amyloidosis, is increasingly recognized in older adults and can mimic common heart failure symptoms.
The blood signal associated with pTau was even more pronounced in patients with amyloidosis who also experienced polyneuropathy – nerve damage causing tingling and numbness. Here’s significant given that many individuals with amyloidosis develop neuropathy before a formal diagnosis is made. The elevated pTau levels could potentially facilitate distinguish amyloid-related neuropathy from more common nerve problems caused by conditions like diabetes.
“Contrary to some views, pTau should not serve as a standalone diagnostic criterion,” Jucker stated. The findings underscore the need for a comprehensive clinical evaluation, considering potential amyloid involvement in other organs, even when a blood test suggests Alzheimer’s disease.
Researchers hypothesize that cells release more of the pTau marker when amyloid deposits cause cellular stress, regardless of location. Tau protein isn’t exclusive to nerve cells in the brain; it’s also found in peripheral nerves, heart muscle, and kidneys. This broader distribution lends biological plausibility to the finding that amyloid deposits anywhere in the body can trigger a pTau response.
The study also acknowledged the potential for kidney disease to influence blood marker levels, as impaired kidney function can lead to increased protein circulation. However, even after adjusting for creatinine – a measure of kidney strain – the core pattern of elevated pTau in amyloidosis patients remained consistent.
A second, independent version of the pTau marker test yielded similar results, strengthening the validity of the findings. Both tests are currently being evaluated for wider use in memory clinics and clinical trials. In one cohort, the second marker accurately distinguished amyloid patients from controls at a rate comparable to the first version.
Notably, pTau levels also began to rise in individuals carrying inherited genetic mutations linked to amyloidosis *before* the onset of symptoms, suggesting the marker could potentially serve as an early warning signal. However, researchers caution that the study size was limited and further investigation is needed to pinpoint the specific organ responsible for releasing the protein.
“Our results could open up new possibilities for diagnosis of systemic amyloidosis,” Jucker said, highlighting the potential for earlier detection. The study, published in Nature Medicine, suggests the blood marker now functions less as a specific Alzheimer’s indicator and more as a general readout of amyloid-related tissue damage, potentially improving diagnosis of amyloidosis while necessitating a more nuanced approach to Alzheimer’s screening.