A drop of blood to detect the progression of Alzheimer's: how the new test approved in the US works

According to the World Health Organization (WHO), “Alzheimer's disease is the most common form of dementia and may account for between 60% and 70% of cases.” A decisive step toward understanding the progression of this disease has just been taken in the United States.

The Food and Drug Administration (FDA) approved for the first time an in vitro blood test specifically designed to evaluate the disease in patients with cognitive impairment. It is a test called Lumipulse G pTau 217/β-Amyloid 1-42 Plasma Ratio, which was incorporated into all clinical laboratories in the country. This official validation marks a paradigm shift: from now on, a simple blood sample will allow physicians to identify early signs and the progression of Alzheimer's without having to resort, initially, to more invasive procedures such as cerebrospinal fluid punctures or brain CT scans.

“Today's approval is an important step forward for Alzheimer's diagnosis, facilitating earlier access to this tool for patients in the United States,” said Dr. Michelle Tarver, director of the FDA's Center for Devices and Radiological Health.

The device, developed by Fujirebio, is not intended for mass or preventive use: it is indicated for adults over 50 years of age who show symptoms of cognitive decline and are already being evaluated by a specialized medical team. In these cases, the test acts as a first step to confirm or rule out the presence of β-amyloid plaques in the brain, one of the most recognized biological signs of Alzheimer's.

The new tool is inserted into a scenario where diagnosis often comes late. Alzheimer's disease develops over years, and in some cases even decades, before symptoms become clear. The lack of accessible, noninvasive diagnostic tools has long left millions of patients without accurate evaluation in the early stages, when available interventions can have the greatest impact.

In fact, in the United States alone, it is estimated that more than 7.2 million people are currently living with Alzheimer's. Projections indicate that this figure could double by 2060.

Researchers see this new test as a way to improve access, reduce clinical uncertainty, and enable treatment pathways more tailored to the patient's profile. For the FDA, the authorization marks a regulatory milestone: until now, similar tests were developed and marketed without its approval, under a legal concept known as "laboratory-developed tests."

This less supervised category allowed private laboratories to offer diagnostic services without sufficient validation, raising concerns among physicians and patient associations. The approval of Lumipulse sets a new standard.

The test is based on the measurement of two key proteins: pTau 217 and β-amyloid 1-42. These proteins circulate in plasma, and their ratios allow us to infer the presence of plaque deposits in the brain, considered one of the clearest signs of Alzheimer's disease.

According to the study that supported the FDA application, the test was tested in a population of 499 patients with signs of cognitive impairment. The results showed a positive predictive value of 92% and a negative predictive value of 97%, a very high level of agreement with traditional diagnostic methods. Only 20% of the cases fell into the gray zone, necessitating the need for further studies.

“Currently, Alzheimer's disease biomarkers are cerebrospinal fluid (CSF) biomarkers (a substance that circulates around and within the brain and spinal cord and is designed to protect against injury) and neuroimaging-based biomarkers. But the future lies in blood-based biomarkers,” Dr. Ricardo Allegri , head of Cognitive Neurology, Neuropsychology, and Neuropsychiatry at Fleni.

“Dementia is a syndrome (a set of signs and symptoms), such as, for example, fever, but Alzheimer's is a disease in which one of the stages is dementia,” the expert neurologist stated. In this regard, he noted that dementia is a global syndrome that can have different profiles, depending on the cause: “Thus, in Alzheimer's, memory loss predominates; in frontotemporal dementia, behavioral disturbances.”

Meanwhile, previously, Dr. Fernando Cáceres, a neurologist, neurorehabilitation specialist, and director of the Institute of Restorative Neurosciences (INERE) that cognitive impairment "is not synonymous with dementia. Mild cognitive impairment does not affect the person's quality of life or independence, as they continue to function with their deficits. On the other hand, dementia is a cognitive impairment that affects a person's social life and independence, and presents psychiatric and psychological symptoms. Therefore, cognitive impairment should not be confused with dementia."

How Alzheimer's Disease Works

Alzheimer's disease affects the brain by damaging its most basic components: neurons. It causes them to fail to fulfill their function and eventually die. The process by which this disease destroys neurons is called neurodegeneration. Its symptoms are cognitive and behavioral, such as memory problems, orientation problems, and confusion, and it is the most common cause of dementia in older adults.

“One in eight people over 65 has Alzheimer's; at 75, two in eight; and at 85, four in eight,” said Dr. Cáceres.

“The paradigmatic symptom of Alzheimer's is memory loss, which is why forgetfulness or lapses in recall are the first warning signs to consider. There are many types of memory, but the most affected are those of recent events, old things; the person remembers them,” said the expert.

In the early stages of Alzheimer's, the most characteristic sign is recent memory loss. According to neurologist Alejandro Andersson, director of the Buenos Aires Institute of Neurology (INBA), the disease begins when the neurons in the hippocampus, responsible for forming new memories, begin to deteriorate due to the accumulation of the beta-amyloid protein. "The type of memory that is first compromised is that which has a time and place,"

This means that the person will forget everyday events, such as not remembering what they had for breakfast, repeating questions, misplacing objects, or not knowing if they took a medication. As the disease progresses, this deterioration extends to other types of memory and cognitive functions, but in the early stages, the impact is concentrated on short-term episodic memory.

Better clinical decisions

The breakthrough validated by the FDA is more than a technical achievement: it represents a change in the way we understand the clinical approach to neurodegenerative diseases. The new test is performed on a blood sample and can be processed on automated equipment such as the Lumipulse G1200, which is already operational in numerous laboratories in the United States.

This automated system can process up to 120 tests per hour, making its application a viable solution within the routine of specialized clinical services. This processing volume shortens wait times for results, which in many cases can determine whether or not a therapeutic strategy is initiated.

The FDA's decision does not imply that the new test completely replaces previous methods. The test does not replace brain imaging or cerebrospinal fluid analysis. However, it is positioned as a highly accurate and low-cost pre-screening test that can guide the next steps in diagnosis. In this sense, it could avoid unnecessary examinations or help select which patients should be referred for more complex studies. For physicians, it represents a diagnostic support tool. For patients, it represents a less invasive and more accessible option.

In parallel with the clinical advancement, the test's approval also had a regulatory impact. In recent years, the United States government has sought to increase control over tests developed in independent laboratories. The official argument was clear: without sufficient validation, patients could receive incorrect diagnoses and miss out on treatments that could have improved their outcomes. However, last March, a federal judge in Texas overturned a rule attempting to restrict the use of this type of test. The lawsuit was filed by the American Association of Clinical Laboratories, which argued that the measure would affect the system's operation.

“The FDA regulations were designed half a century ago, when tests created and used by a single laboratory were simple, low-volume, and geared toward local needs,” explained health spokespersons.

Today, in a context where neurodegenerative diseases are gaining ground among public health priorities, the development of scientifically valid tests takes on another dimension. Therefore, the test's approval was also interpreted as a signal: Alzheimer's diagnosis is entering a new era of accuracy, speed, and official validation.

The test also received “Breakthrough Device Designation” from the FDA, a category reserved for technologies that represent a significant advance in areas with unmet medical needs. This designation enables a faster regulatory pathway and recognizes the test's potential to improve medical care in a time-sensitive field.

The scientific community, patients, and organizations that support those living with Alzheimer's received the news with optimism. Dementia currently affects more than 55 million people worldwide. Ten million new cases are diagnosed each year. The majority are Alzheimer's, a disease that accounts for between 60% and 70% of all cases. Early detection does not guarantee a cure, but it does allow for better decision-making.

With this validation, the Lumipulse test could transform the first step in diagnosis in the future. Instead of clinical assumptions based solely on symptoms, physicians will have an objective test that indicates the presence or absence of one of the clearest biological hallmarks of the disease.

When this test is open to the entire community, the information will allow for more precise treatment initiation, more consistent follow-up, and long-term care planning.

It's worth remembering that while Alzheimer's has no cure, there are drugs that can mitigate symptoms, delay progression, and improve quality of life. However, their effectiveness is limited in advanced stages.

In this regard, Santiago Tizio, head of the Neurology Department at the Spanish Hospital in La Plata, “Today, the most innovative treatments on the market are those designed to eliminate amyloid beta. In this regard, we find aducanumab, which is the first molecule studied. Basically, two large studies were conducted. In the first, it was found to be capable of eliminating amyloid beta and inducing an improvement in the functional status of patients. In the second study, although they were able to replicate the result regarding the elimination of amyloid beta, they couldn't demonstrate that it was beneficial for patients, and despite having been launched on the market, it was withdrawn shortly after.”

Tizio referred to monoclonal antibodies, "which are aimed at eliminating the beta-amyloid protein. From a pathophysiological perspective, Alzheimer's, which is a neurodegenerative disease, is characterized by the accumulation of beta-amyloid plaques and also by the presence of neurofibrillary tangles of the TAU protein, which is normally present in neurons and participates in the stability of the cytoskeleton, that is, the cellular skeleton, which is composed of proteins and protein aggregates called microtubules. These microtubules, in addition to having a structural function, play a role in the transport of molecules from one place to another."