Blood may hold the key to unlocking Alzheimer’s diagnosis

Research has given us a more in-depth understanding of Alzheimer’s disease in recent years. It’s now known that there are biological changes linked to the condition. This new and advanced knowledge has led to new treatment options, as well as revised diagnostic criteria. In June 2024, an Alzheimer’s Association Workgroup released revised criteria for the diagnosis and staging of Alzheimer’s disease that incorporates recent research developments.^[]

The updated criteria includes an advanced biomarker classification system using blood-based markers. These biomarkers are grouped into three categories: core biomarkers of Alzheimer’s disease neuropathic change (ADNCP), non-specific biomarkers that are important in Alzheimer’s disease pathogenesis and also seen in multiple degenerative brain conditions, and biomarkers of common Alzheimer’s comorbidities.

According to the most recent Alzheimer’s research, changes to Core 1 biomarkers begin before symptoms of the condition are presented. The progression of changes to biomarkers leads to the presentation and progression of expected Alzheimer’s symptoms, including memory loss and cognitive difficulty. In its revised diagnostic standards, the Alzheimer’s Association Workgroup concluded that the presence of these blood-based biomarkers can be sufficient to diagnose Alzheimer’s: “AD is defined by its unique neuropathologic findings; therefore, detection of AD neuropathologic change by biomarkers is equivalent to diagnosing the disease.”

Biology-based diagnostics and new treatments

Currently available Alzheimer’s treatments provide symptom relief but do not slow down disease progression. Emerging treatments aim to change this by targeting biological factors. For instance, as of July 2024, three anti-amyloid immunotherapy treatments have been approved by the United States Food and Drug Administration.^[] Diagnostic results showing the buildup of amyloid plaque, a Core 1 biomarker, are essential for the use of these drugs. 

Neuroradiologist Clifford R. Jack, Jr., MD, Professor of Radiology at the Mayo Clinic and a lead author of the Alzheimer’s Association Workgroup’s new criteria, explains: “These updates to the diagnostic criteria are needed now because we know more about the underlying biology of Alzheimer’s, and we are able to measure those changes. Treatments that target one of these processes have been approved by regulators, and biomarker proof that the underlying biology is present must be confirmed to be eligible for treatment.”

Additionally, traditional symptom-based diagnostic criteria can overlap with other neurologic disorders and conditions. Biomarker testing has the potential to allow for a more definitive diagnosis.^[][]

Limitations and controversies

The revised criteria aren’t intended to be used as a formal guideline for clinicians.^[] The Alzheimer’s Association Workgroup emphasizes that clinical judgment is still key to diagnosing Alzheimer’s. Although findings show that Core 1 biomarkers change before symptoms are present, researchers are not currently recommending biomarker testing for asymptomatic individuals. 

The Alzheimer’s Association Workgroup writes, “The biologically based diagnosis of Alzheimer’s disease (AD) is meant to assist rather than supplant the clinical evaluation of individuals with cognitive impairment.”

Some healthcare experts have raised concerns about new diagnostic criteria for Alzheimer’s. For instance, in 2023, the American Geriatrics Society (AGS) published a response to earlier suggestions made by the Alzheimer’s Association Workgroup about biomarker-based diagnostics.^[] In its response, the AGS expressed hesitation about diagnosing asymptomatic individuals with Alzheimer’s, writing, “AGS is concerned about the rationale of making Core 1 biomarkers the basis for clinical diagnosis or labeling all people with amyloid biomarkers as ‘having AD.’ Such action ignores decades of social science research on the often-adverse effects of labeling, including promotion of stigma, and begs the question as to what purposes biomarker-based diagnosis might serve in patient care.”

It’s been stated that biomarker testing has the potential to help with early detection and treatment of Alzheimer’s.^[] At this time, however, biomarker testing isn’t being used to diagnose individuals without symptoms. The AGS, the Alzheimer’s Association Workgroup, and other leading organizations agree that further research and clinical testing is vital.^[][][]