Alzheimer’s Diagnosis: The Need for Easier Tests
Diagnosing Alzheimer’s disease (AD) currently often requires complex and expensive methods like PET scans or spinal fluid tests. These procedures can be invasive, costly, and not easily accessible for everyone, especially in diverse and global populations. With over 20% of AD patients worldwide being Chinese, there’s a significant need to understand how well blood-based tests perform across different ethnic groups. Recent research is rapidly advancing the field, focusing on identifying reliable biomarkers in the blood that could revolutionize how AD is detected, monitored, and even predicted years before symptoms become severe.
Plasma Tau Biomarkers: A Promising Approach
Tau proteins are crucial in the brain, but abnormal forms, particularly phosphorylated tau (p-tau), build up in AD, forming tangles. Measuring p-tau levels in the blood is a key area of research for developing simple, accessible AD tests. A recent comprehensive evaluation in a multicenter study, including significant Chinese and North American cohorts, explored the effectiveness of various plasma tau biomarkers in detecting and monitoring AD across a multiethnic aging population of 1,085 participants.
p-tau217: The Standout Biomarker
The evaluation highlighted one plasma biomarker, p-tau217, as particularly effective. This study found that plasma p-tau217 performed best among the tested biomarkers in accurately identifying the presence of amyloid-beta (Aβ) and tau pathology as seen on PET scans, covering the entire spectrum of AD progression. Crucially, levels of plasma p-tau217 also correlated significantly with various outcomes related to Alzheimer’s disease.
Further analysis using a specific two-cutoff approach revealed that individuals with intermediate plasma p-tau217 levels experienced rapid accumulation of both Aβ and tau pathology in the brain, alongside accelerated decline in metabolism and cognitive function. Moreover, increasing plasma p-tau217 levels were strongly linked to faster changes over time in Aβ-PET, tau-PET, and markers of neurodegeneration. These findings strongly suggest that plasma p-tau217 is superior for detecting multiple aspects of AD-related brain changes and tracking the disease as it progresses.
Translating Blood Tests to Clinic: Guiding Patient Care
Beyond just detecting pathology, blood tests like p-tau217 are being evaluated for their practical utility in clinical decision-making. Large-scale studies involving thousands of individuals demonstrate how interpreting plasma p-tau217 results alongside clinical information – specifically age and the individual’s clinical presentation (e.g., probable AD dementia, mild cognitive impairment (MCI), or other non-AD syndromes) – can provide a valuable framework for diagnosing amyloid-beta pathology at the individual level.
For instance, in individuals with a clinical diagnosis of probable AD dementia, a high plasma p-tau217 level has a very high probability (>95%) of indicating underlying Aβ+ pathology, potentially reducing the need for confirmatory PET or CSF tests. In those with MCI, the significance of a positive or negative p-tau217 test changes with age; it becomes highly reliable for “ruling in” Aβ+ in older adults with MCI, while a negative result is more useful for “ruling out” Aβ+ in younger individuals with MCI or those with clinical presentations suggesting non-AD forms of dementia. This tailored approach, potentially further refined by considering APOE ε4 genetic status, could significantly streamline the identification of patients eligible for emerging anti-amyloid therapies by avoiding unnecessary invasive procedures for many.
Predicting Future Risk in Healthy Adults
Research in community-based populations, including studies with long-term follow-up, is also exploring the ability of blood biomarkers like p-tau217 to predict the future risk of developing AD dementia in cognitively healthy older adults. While elevated levels of p-tau181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) have been associated with an increased hazard for incident dementia, their predictive power in this setting is more nuanced.
These biomarkers show high Negative Predictive Values (NPVs), meaning a low level can reliably indicate a low risk of developing dementia over the next decade. This has significant potential for counseling individuals and reducing anxiety. However, their Positive Predictive Values (PPVs) for screening cognitively unimpaired individuals remain relatively low when used alone, suggesting they are not yet sufficient as standalone screening tools for the general population. Combining multiple biomarkers may improve predictive accuracy.
Beyond Amyloid: Tracking Neurodegeneration with BD-tau
While p-tau isoforms like p-tau217 are excellent markers for amyloid-beta pathology and associated tau tangle pathology, another promising blood biomarker, Brain-Derived Tau (BD-tau), is emerging as a more specific marker for AD-type neurodegeneration itself. Studies show blood BD-tau levels are elevated in individuals with both Aβ pathology and neurodegeneration and correlate well with neurodegeneration markers in spinal fluid.
Crucially, blood BD-tau predicts the rate of future brain atrophy and cognitive decline, unlike general markers like NfL. A significant advantage of BD-tau is its relative independence from factors that can affect other biomarkers, such as age, kidney function, or common health conditions, making it potentially more specific to the AD process. Combining plasma p-tau (as an Aβ marker) with plasma BD-tau (as a neurodegeneration marker) allows for a blood-based classification system mirroring the A/N (Amyloid/Neurodegeneration) framework used in research, which can effectively stratify individuals based on their risk of cognitive decline and brain shrinkage.
The Future of Blood-Based AD Testing
Collectively, this body of research underscores the transformative potential of blood-based biomarkers, particularly plasma p-tau217 and the emerging BD-tau, for Alzheimer’s disease. These tests offer a less invasive, potentially more affordable, and more accessible path forward for widespread AD detection, accurate diagnosis, monitoring disease progression, predicting future risk, and selecting patients for clinical trials and therapies across diverse global populations. While challenges remain in refining their use as standalone screening tools in certain contexts, their utility in clinical diagnosis and risk stratification is rapidly becoming clear.
