Lab precision in Alzheimer’s diagnosis

• The aging global population means the incidence of age-related diseases such as Alzheimer's is set to rise dramatically
• Advances in Alzheimer’s care mean people with the disease can be diagnosed and treated at an early stage, when it is possible to delay cognitive decline
• Clinicians and laboratories need to work together to achieve a timely and accurate diagnosis

The global population is aging, resulting in increasing numbers of age-related diseases, such as dementia. Today, there are 55 million cases of dementia worldwide, and this number is estimated to rise to 139 million by 2050.¹ The most common form of dementia, Alzheimer’s disease, accounts for up to 80% of cases.² Symptoms of early-stage Alzheimer’s disease are mild. Still, the progressive nature of the disease means that over a number of years, memory and cognitive skills will worsen, and people will lose their ability to be independent.³ 

Although there is no cure for Alzheimer’s, in recent years, there have been advances in diagnostic and digital tools, along with treatments that can delay progression for people in the early stages of the disease.^4,5

At EuroMedLab 2025, Dr. Pablo Martínez-Lage, a Neurologist at Foundation CITA Alzheimer, in Spain, and Dr Wibke Johannis, a Senior Physician at Universitätsklinik Köln LFI, in Germany, spoke about the importance of a multidisciplinary approach to early-stage Alzheimer’s diagnosis.

Dr. Martínez-Lage outlines the importance of timely diagnosis in Alzheimer’s: “We now know that the movie of Alzheimer's Disease has an end, which is dementia, and dependency. But before that, the disease has gone through different stages.” Someone with the initial symptoms of Alzheimer’s can live a fairly normal and independent life, and by diagnosing patients at this stage, there are options available. “We can do prevention. We can do things to delay the appearance of dependency,” explains Dr. Martínez-Lage. 

Traditionally, to diagnose Alzheimer’s, clinicians had to be certain of dementia first, and then, through blood tests and imaging, sought to rule out other diagnoses such as tumor or vascular pathology. “We were only right in two out of three cases,” Dr. Martínez-Lage acknowledges. Now the diagnostic paradigm has completely changed, he explains, “Now we don't have to wait until dependence. We can look at the first symptoms, and then if someone with these symptoms has the biology of Alzheimer's disease in his or her brain, then we can make the diagnosis. This is the clinical, biological approach.”

The biology of Alzheimer’s revolves around two key players – amyloid and tau pathology. “There are other stars in the movie, like vascular pathology and inflammation, but the biology to be ascertained is amyloid and tau,” explains Dr. Martínez-Lage. A revolution in Alzheimer’s disease came with molecular imaging, particularly PET scans, allowing clinicians to see the presence of these biomarkers in the brain. However, PET scans are prohibitively expensive for many healthcare systems. 

“The good news is that we have another beautiful window to the brain if we think that there is a balance between the brain tissue, the interstitial fluid in the brain, the cerebrospinal fluid (CSF) and blood,” says Dr. Martínez-Lage, “This balance allows us to look at the brain by doing a lumbar puncture.” Similar to an epidural anesthetic, the lumbar puncture is a routine procedure that is much more accessible for healthcare systems. 

Biomarker levels in CSF, and the relationship between them, have been shown to reflect measurements achieved in PET scans, and therefore clinicians are able to use this information to support a clinical diagnosis, and improve the accuracy of diagnosis in people with symptoms of early-stage Alzheimer’s.

“As I said, the paradigm has changed,” says Dr. Martínez-Lage, explaining, “We can do the diagnosis now in a state where someone has only some memory deficits, but is still living a normal life.” By diagnosing at this stage, in a timely way, there is a chance to provide treatment and preventative care. “Collaboration between neurologists and lab medicine experts is not only important because of treatment, but also because we are giving people the chance to plan their future. We are giving them the chance to participate in the diagnostic and therapeutic process,” says Dr. Martínez-Lage.  

Dr. Johannis agrees that collaboration is critical to navigate new technologies and achieve the best for patients. Her lab runs weekly clinical case conferences with physicians to discuss patient cases, and she explains this allows them, “To bridge the gap between clinical needs and the laboratory precision medicine.” 

It was within this setting that she communicated to clinicians about a change in the technology the lab was using, which would enable more efficient biomarker testing for Alzheimer’s, but would alter the way they interacted with the lab. 

Dr. Johannis explains pre-analytics is a ‘really, really major issue’ when analyzing Alzheimer biomarkers, and within this process, there are three critical phases. First, the clinicians obtain a CSF sample via lumbar puncture, second is the transport phase, and third is a lab-based pre-analytical phase. 

At each stage, there are associated pre-analytical risks. While lumbar puncture itself is a standard procedure for clinicians, collecting CSF for Alzheimer’s biomarker analysis requires specific tubes and defined fill volumes to ensure accurate results. Dr. Johannis acknowledges that because of these requirements, there can occasionally be issues with sample handling, but that communication between clinicians and the laboratory is key to overcoming them. “Once clinicians are aware of the fact that using the wrong tube, or not filling it up to the top, could result in a loss of amyloid and produce a false positive result, we found the process works much better,” she explains. 

The transport phase is less problematic for Dr. Johannis, as the biomarkers are relatively stable and her lab and clinics are nearby. She notes  that samples should be transported within the recommended time window, and cooling may be required depending on the duration and environmental conditions. 

Due to the lab transitioning to newer technology that supports a more standardised workflow to perform the assays, Dr Johannis says the third stage is “actually very, very easy” and no longer requires extensive manual handling. This technology-driven shift reduces the variability associated with manual sample preparation and helps streamline the process, although staff still need time to adjust to the updated approach. She explains, “They were used to opening samples. They were used to splitting samples. They were used to putting the CSF samples into the freezer. All these steps aren’t to be performed anymore because they would also result in the loss of amyloid.”

While transitioning to a new workflow always needs specific considerations to bear in mind, Dr. Johannis reports strong confidence in the precision and accuracy of the biomarker measurements.“We’re confident that our lab measurements are precise, and that they are accurate and that we’re producing reliable results.” These improvements support clinicians by providing reliable biomarker information for diagnosis.  

Dr. Martínez-Lage outlines one such example from his clinic: 

• A 75-year-old male presented with memory problems such as difficulty recalling recent events, and forgetting conversations or things that happened the day before
• Symptoms had been going on for one or two years, but otherwise, he was living a normal life. He was doing errands, driving, taking care of his grandchildren, etc. 
• An MRI showed vascular disease mostly in the frontal lobe, but also some atrophy in the temporal lobe, which is typical of Alzheimer's
• Because the prognosis for vascular disease and Alzheimer’s is completely different, the team decided to check for biomarkers
• Biomarker analysis showed amyloid and tau abnormalities consistent with an Alzheimer’s disease profile

A diagnosis of Alzheimer’s disease allowed clinicians to not only prescribe treatment, but also to recommend supportive interventions, including nutritional supplementation and cognitive therapy with the goal of maintaining the patient’s quality of life. A goal Dr. Martínez-Lage was pleased to achieve: “We got it. We saw him a year later, and he was still living a normal life. Having some memory problems, but quite happy.”  

Scientific advances in Alzheimer’s diagnosis are reflected in revised criteria published by the Alzheimer’s Association in 2024, which recommend defining the disease biologically rather than by clinical syndrome(s), stating that, “The disease is diagnosed in individuals by abnormalities on core biomarkers.”⁶

However, at this stage, the advice is only for people who already have symptoms of Alzheimer’s. Given the complexity of the brain pathology, Dr. Martínez-Lage points out that it is common for more than one pathology to co-exist, as in the case study patient with both Alzheimer’s and vascular disease. For this reason, he explains that biomarkers are important to assist in diagnosis but should not be used in isolation. Instead, “a multidisciplinary approach between clinicians, laboratory medicine doctors, and neuroimaging doctors” is key.