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What Blood Biomarkers Can – and Can’t – Tell Us About Alzheimer’s

Digital illustration of a brain with fragments symbolizing the focus on Alzheimer's biomarkers, with white text reading "Biomarkers in Focus" overlayed.
Credit: Technology Networks.
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Efforts to diagnose Alzheimer’s disease earlier and more easily are picking up pace, especially with the rise of blood-based biomarkers.


These tests measure proteins such as pTau217 and pTau181 in the blood, and are being explored as simpler, less invasive alternatives to traditional diagnostic methods. These markers mirror the same pathological features found in brain tissue or CSF. Researchers hope they could help detect signs of disease many years before symptoms begin, potentially at a stage where therapeutic intervention may slow progression.


Historically, Alzheimer’s diagnosis has relied on a combination of clinical assessments and more invasive tests. These include neuroimaging methods such as PET scans to detect amyloid plaques and lumbar puncture procedures to collect cerebrospinal fluid (CSF), where beta-amyloid and tau levels can be measured. These markers have been used for years to support diagnosis, particularly in research settings and memory clinics.


“Protein aggregates of beta-amyloid and of the tau protein in the brain are the key pathological hallmarks that define Alzheimer’s disease,” Dr. Patrick Oeckl, a neuroscientist at the German Center for Neurodegenerative Diseases, told Technology Networks. Oeckl leads a research group focused on translational biomarker development using advanced mass spectrometry techniques, and has over 15 years of experience in the field.


According to Oeckl, biomarker changes can be detected long before symptoms begin. “Exact numbers are difficult to predict,” he said, “but the current data indicate that changes might be measured as early as 20 years before the clinical diagnosis of Alzheimer’s disease.”


While blood tests may be easier to use, the fluid they rely on brings a different set of challenges.


This article explores the scientific potential, limitations and future of blood-based biomarkers for Alzheimer’s, and why fluid context still matters.

The promise of blood-based Alzheimer’s biomarkers

Blood-based biomarkers for Alzheimer’s typically involve measuring abnormal forms of tau or beta-amyloid proteins in the bloodstream.


Over the past decade, advances in assay sensitivity, particularly for forms such as pTau217 and pTau181, have made it possible to detect these proteins at very low concentrations in plasma.


This has raised hopes for routine, non-invasive screening tools that could complement or even replace more invasive procedures.

“These biomarkers are very promising and studies indicate that their performance can be identical to the measurement in cerebrospinal fluid,” Oeckl said.

Another blood-based biomarker under investigation is beta-synuclein, a protein found at synapses that is released into the bloodstream when these connections begin to deteriorate.


A 2025 study led by Oeckl found that blood levels of beta-synuclein began to rise ~11 years before the expected onset of dementia symptoms in individuals with a genetic predisposition to Alzheimer’s. The research followed participants in the Dominantly Inherited Alzheimer’s Network (DIAN), combining biomarker data with cognitive tests and brain scans.


While the study focused on familial Alzheimer’s disease, Oeckl noted that similar patterns may apply to sporadic cases. If confirmed, beta-synuclein could be used not just for early diagnosis, but also to monitor treatment effects in trials targeting neurodegeneration.


“I am excited to see if synaptic biomarkers such as beta-synuclein can be used to monitor treatment effects of novel anti-amyloid and other drugs,” said Oeckl.

Fluid-specific performance and diagnostic risk

Not all biomarkers perform equally well across different biofluids. CSF, which is in direct contact with the brain and spinal cord, tends to provide a more specific picture of central nervous system pathology. Blood, however, circulates throughout the entire body and contains proteins from multiple organs and tissues, which can interfere with interpretation.

“Some biomarkers show equally good performance in CSF and blood,” Oeckl said, “whereas for others, especially those with expression also in non-brain tissue, measurement in CSF is better.”

One example is tau, a key Alzheimer’s-related protein. Research has shown that tau proteins, including pTau217 and pTau181, can also be released from muscle tissue in certain diseases. In a recent study, blood levels of these proteins were elevated not only in Alzheimer’s disease patients but also in individuals with amyotrophic lateral sclerosis (ALS), a neurodegenerative muscle disease.


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“It is not yet completely clear how other diseases of muscle tissue affect blood levels of pTau217 and pTau181,” Oeckl noted.


Further investigation using muscle biopsies revealed the presence of these phosphorylated tau proteins in muscle tissue, with ALS samples showing increased pTau reactivity in atrophic muscle fibers. These findings suggest that elevated blood pTau levels might reflect pathology outside the brain, such as muscle degeneration, underscoring the importance of careful interpretation of blood biomarker results.


A blood test therefore, might show elevated tau levels that are unrelated to Alzheimer’s pathology, pointing to the disease when the signal is coming from somewhere else entirely.


This is a key reason why CSF often gives a more accurate picture; it reflects what’s happening in the brain, without interference from the rest of the body.

The future of blood-based biomarkers

Despite these limitations, blood biomarkers are advancing quickly, and researchers continue to explore their role in diagnostic workflows.


“I’m most excited about how and if blood biomarkers such as pTau217 will be integrated in clinical routine,” said Oeckl. “Especially in primary care and for preclinical diagnosis.”


One proposed approach is to use these biomarkers in a tiered testing model. Blood tests could be used for broad initial screening, followed by more specific confirmation through CSF analysis or neuroimaging when needed. This could expand access to early detection without relying solely on more invasive or costly methods.


The growing promise of blood-based biomarkers is now also beginning to translate into real-world clinical tools. In May 2025, the US Food and Drug Administration cleared the first blood test to aid in the diagnosis of Alzheimer’s disease: the Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio. Designed for use in adults aged 55 and older with symptoms of cognitive decline, the test measures levels of pTau217 and β-amyloid 1-42 in plasma to infer the presence of amyloid plaques in the brain.


 While not a stand-alone diagnostic tool, this FDA-cleared test provides a less invasive and potentially more accessible alternative to PET imaging or lumbar punctures – representing an important step toward broader clinical implementation of blood-based biomarkers.