Alzheimer’s disease has long been diagnosed based on cognitive symptoms until recently. Brain imaging scans and cerebrospinal fluid assays have been used for diagnosis, but they are expensive, invasive, or not easily accessible. Recent technological advances have led to the development of blood-based biomarkers that could potentially allow for early and inexpensive diagnosis of Alzheimer’s. However, challenges still need to be addressed before these biomarkers can be used in routine clinical care. The disease, affecting an estimated 7 million individuals in the US, is progressive, leading to cognitive and functional deterioration over time.
The FDA has recently approved the first three disease-modifying treatments for Alzheimer’s, highlighting the importance of early diagnosis. These drugs are most effective in individuals in the early stages of the disease, making early diagnosis vital. Traditional diagnostic methods based on clinical symptoms have limitations, with around 25-30% of individuals not receiving an appropriate diagnosis in specialized clinics. Therefore, a shift towards a focus on pathological changes in the brain has been recommended for Alzheimer’s diagnosis.
The ATN framework recommends Alzheimer’s diagnosis based on biomarkers for beta-amyloid deposits, tau neurofibrillary tangles, and neurodegeneration. Current biomarkers are accurate but expensive and invasive, limiting their use in routine clinical care. Blood-based biomarkers offer a more accessible and cost-effective alternative, with recent developments showing promise in reducing recruitment costs for clinical trials and facilitating monitoring of treatment outcomes. While not yet ready for standalone use, they may soon be used in clinics alongside other diagnostic methods.
The development of blood-based biomarkers for Alzheimer’s has included assessing beta-amyloid levels and different species of phosphorylated tau proteins. These markers can help identify individuals with preclinical Alzheimer’s and track disease progression. Additional biomarkers, such as neurofilament light and glial fibrillary acidic protein, may also aid in diagnosing and monitoring Alzheimer’s disease. Challenges remain in deploying these biomarkers in clinical settings, including validation, standardization, and interpretation of results.
Ongoing studies are addressing concerns about the real-world performance of blood-based biomarkers in diverse populations. Standardization of assays and guidelines for their use are needed, as well as validation of their accuracy and correlation with existing diagnostic methods. Despite these challenges, the potential impact of blood-based biomarkers on early Alzheimer’s diagnosis and treatment monitoring is significant. Pragmatic and logistical challenges to the adoption of these tests in clinical settings are being addressed, with future accessibility expected to improve.
