Breaking Diagnostic Barriers in Alzheimer’s With Fluid Biomarkers

Alzheimer’s is a devastating disease for the impacted person and their family. It is a major public health challenge, as currently, more than 55 million people live with dementia, of which Alzheimer’s is the most prevalent form, and this is expected to rise to nearly 153 million by 2050. This figure is more than double the entire population of Italy.

Early and accurate diagnosis is critical for improving outcomes for people with Alzheimer’s disease. As the disease progresses, the cost of care rises significantly, placing a considerable burden on caregivers and health systems. Timely diagnosis provides individuals and their loved ones with the opportunity to plan for care, make lifestyle changes and access treatment options to help manage the disease.

While treatment has previously been focused on managing symptoms, recent advancements with novel disease-modifying therapies (DMTs) in early Alzheimer's offer the potential to slow disease progression. This makes it more important than ever before to provide appropriate tools for early and accurate diagnosis. The earlier a diagnosis can be made, the more effective these treatments can be.

However, barriers to diagnosis exist across the globe. Up to 75% of people living with symptoms of Alzheimer’s disease have not been diagnosed, and those who have received a diagnosis have often waited up to 2–3 years to get one.

CSF biomarkers represent a highly accurate diagnostic tool that can enable timely and early diagnosis for Alzheimer's disease patients. 

CSF biomarker tests are gaining traction in Alzheimer’s diagnosis because they are reflective of the hallmark pathological proteins in Alzheimer’s, helping clinicians to objectively determine the disease biologically and facilitate a diagnosis of inclusion.

Where previously the diagnosis of Alzheimer’s has largely been one of exclusion (i.e., ruling out non-Alzheimer’s causes of symptoms) based on several evaluations including various cognitive exams, routine laboratory tests and neuroimaging – CSF biomarker tests take a new approach. These tests directly measure the hallmarks of Alzheimer's disease, such as beta-amyloid and tau proteins in a patient’s CSF. CSF biomarkers offer a more accurate means of diagnosis and inform risk of future cognitive decline within two years.

CSF biomarkers enable Alzheimer’s pathology to be detected in the early stages of the disease, enabling earlier intervention with DMTs to slow disease progression and improve patient outcomes. Changes in CSF biomarker levels can also be monitored to track the progression of the disease and potentially monitor the effectiveness of new treatments.

One of the main barriers to broader adoption is the need for a lumbar puncture to collect CSF, a technique similar to an epidural commonly used during labor, which, although safe and generally very well tolerated, may be less popular than blood tests for instance. However, a recent study from a memory clinic in London has shown that CSF testing is highly acceptable with >95% of participants reporting that they were very satisfied. Clinicians require adequate training and facilities to perform lumbar punctures and to interpret CSF biomarker results in routine clinical practice. Sample handling, test methods and interpretation of results also need to be consistent between laboratories. CSF biomarker testing is generally more accessible and cost-effective compared to the other approved confirmatory diagnostic method (amyloid-positron emission tomography (PET) scans), and has the advantage of being radiation-free.

Overall, CSF biomarkers offer significant advantages for the early and accurate diagnosis of Alzheimer’s, providing objective insights into brain pathology. Their broader adoption hinges on overcoming the perceived invasiveness of lumbar puncture, improving clinician education and confidence and achieving greater standardization across testing facilities. 

CSF biomarker tests are highly concordant with amyloid PET scan imaging and can provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain. They can also detect both amyloid and tau biomarkers from one draw, with no exposure to radiation. CSF analysis can detect changes in amyloid-beta and tau proteins before significant amyloid plaque buildup or brain atrophy are visible on other imaging, allowing for earlier detection of disease.

The high cost, limited availability and risk of patient exposure to radioactivity restrict the use and accessibility of PET. In addition, evaluating both amyloid and tau Alzheimer’s biomarkers using PET requires multiple appointments and procedures.

CSF biomarkers offer a highly accurate tool for the diagnosis of Alzheimer’s disease, enabling Alzheimer’s pathology to be detected in the earliest stages of the disease.

These tests are more accessible than PET scan imaging and will be increasingly used as a diagnostic tool in the future. However, we also see blood-based biomarkers (BBBMs) playing a critical role in early diagnosis in both primary and secondary care settings. BBBMs offer a minimally invasive, accurate, cost-effective and healthcare-agnostic tool to improve the accessibility and acceptability of diagnosis of Alzheimer’s and facilitate earlier treatment. In the near future, BBBMs and CSF biomarkers will work hand in hand to enhance the accuracy and efficiency of diagnosis, providing physicians with the necessary information to make the best decision, for the right patient at the right time.