Alzheimer’s disease is a progressive neurodegenerative disorder that results in loss of memory, thinking skills and ability to carry out daily activities. As of 2022, Alzheimer’s disease affects more than 6 million Americans and is the 6th leading cause of death in the United States. Currently, diagnosis of Alzheimer’s disease is based on medical history, cognitive testing, imaging of the brain and spinal fluid analysis. However, these methods are expensive, invasive and cannot detect Alzheimer’s disease until symptoms appear, which is usually years after the disease process has started in the brain. This has led to a major research effort to develop blood-based biomarker tests that could allow earlier and less invasive detection of Alzheimer’s disease. In this article, we will explore the following questions:
What is Alzheimer’s disease?
Why do we need blood tests for Alzheimer’s disease?
What biomarkers are being studied for Alzheimer’s disease blood tests?
How accurate are current experimental Alzheimer’s blood tests?
What are the limitations and challenges of developing Alzheimer’s blood tests?
Could Alzheimer’s blood tests lead to new treatments?
Conclusion
What is Alzheimer’s disease?
Alzheimer’s disease was first described in 1906 by Dr. Alois Alzheimer. It is characterized by buildup of abnormal proteins called amyloid beta and tau in the brain that form plaques and tangles. This leads to loss of connections between nerve cells and eventually cell death. The earliest symptom is usually difficulty remembering recent events and conversations. As the disease progresses over years, memory loss becomes more severe, language skills decline, personality changes emerge and patients lose the ability to care for themselves. Ultimately, Alzheimer’s disease is fatal.
Why do we need blood tests for Alzheimer’s disease?
There are several reasons blood tests for Alzheimer’s disease are needed:
Earlier diagnosis
Currently Alzheimer’s disease cannot be definitively diagnosed until autopsy after death. It can only be diagnosed in living patients based on symptoms when they become severe enough to interfere with daily functioning. This is usually years after Alzheimer’s pathology has started accumulating in the brain. Blood tests could allow detection of Alzheimer’s disease earlier, before symptoms appear, which could open a window for interventions to slow the disease process.
Less invasive diagnosis
Current diagnostic methods like cerebrospinal fluid collection and positron emission tomography (PET) brain imaging are expensive, invasive and inconvenient for patients. A simple blood draw is much less invasive.
Wider screening
Blood tests would allow screening a much wider population for Alzheimer’s risk and changes. This could help identify candidates for preventive interventions and clinical trials of new Alzheimer’s drugs earlier.
Aid drug development
Reliable blood biomarkers could also accelerate Alzheimer’s drug development by providing quantifiable indicators of drug effects in clinical trials. They could show whether an experimental treatment is actually altering Alzheimer’s disease pathology in the brain.
Lower costs
Blood tests are expected to be much lower cost than current diagnostic methods like PET imaging and cerebrospinal fluid analysis. This would make Alzheimer’s diagnosis more accessible.
What biomarkers are being studied for Alzheimer’s disease blood tests?
The two hallmark pathologies in the Alzheimer’s disease brain are accumulation of amyloid beta protein into plaques and tau protein into neurofibrillary tangles. The leading blood test approaches analyze levels of these proteins or their metabolites in blood or plasma as biomarkers:
Amyloid beta
Amyloid precursor protein is cleaved into smaller amyloid beta fragments that aggregate into plaques in the Alzheimer’s brain. Several forms of amyloid beta are found in blood including AB40, AB42 and their ratio. Levels of these amyloid beta peptides in blood and plasma are being studied intensively as potential biomarkers.
Tau
Tau proteins normally stabilize microtubules in nerve cells. In Alzheimer’s, they become hyperphosphorylated and accumulate into neurofibrillary tangles inside neurons. Levels of total tau and phosphorylated tau in blood are being evaluated as possible biomarkers.
Other proteins
Levels of other proteins involved in Alzheimer’s pathology like neuronal injury marker neurofilament light chain protein are also being studied in blood tests. Proteomic studies are discovering numerous other candidate protein biomarkers in blood.
Genetic markers
Certain genetic mutations like APOE e4 raise Alzheimer’s disease risk. Panels incorporating genetic and blood protein biomarkers are being developed.
| Biomarker | Description |
|---|---|
| Amyloid beta peptides | AB40, AB42 levels and ratio in blood |
| Tau proteins | Total tau, phosphorylated tau |
| Neurofilament light chain | Neuronal injury marker |
| APOE e4 | Alzheimer’s genetic risk allele |
How accurate are current experimental Alzheimer’s blood tests?
Dozens of research groups and companies are working to develop Alzheimer’s disease blood tests. Most of these tests are still in early experimental stages. Their accuracy is being optimized and evaluated in clinical studies. Some examples:
Washington University test
A blood test developed at Washington University in St. Louis detected amyloid beta and tau with over 90% accuracy compared to PET brain imaging in 175 individuals. The test could distinguish Alzheimer’s patients from controls and also predict onset of Alzheimer’s symptoms.
Finnish study
In a 2019 Finnish study, measuring two forms of amyloid beta in plasma could detect early Alzheimer’s pathology with 79% accuracy. The blood test performed similarly to expensive PET brain imaging for detecting amyloid buildup.
Roche Elecsys amyloid test
The Elecsys amyloid beta test developed by Roche diagnostics could identify Alzheimer’s patients with 96% agreement to PET imaging in a preliminary study. The company plans to launch the test commercially pending regulatory approval.
Further improvement needed
While these results are promising, most published studies are small. The reported accuracy of experimental Alzheimer’s blood tests varies widely between studies. Larger clinical validation is still needed to establish their true detection performance. Sensitivity for early disease stages remains a challenge. Continued research to refine and combine biomarkers is ongoing to improve test accuracy.
What are the limitations and challenges of developing Alzheimer’s blood tests?
While Alzheimer’s blood biomarkers show promise, there are still significant limitations and challenges:
No single perfect biomarker
There is likely no single protein or molecule biomarker in blood that can perfectly diagnose Alzheimer’s disease. Combining multiple biomarkers and optimized analysis techniques will be necessary.
Overlap with other diseases
Biomarker changes like amyloid buildup and tau also occur in other neurological disorders. Tests may not always distinguish Alzheimer’s from other causes of dementia.
Early disease detection
Detecting Alzheimer’s pathology during preclinical or early phases before symptoms appear remains technically challenging. Current experimental tests often have low sensitivity in very early disease.
Individual variability
There is heterogeneity in blood biomarker levels between individuals. Finding optimal normal range thresholds for biomarkers to identify Alzheimer’s disease is difficult.
Effects of medication
Some Alzheimer’s medications alter biomarker levels. This could complicate interpreting test results for monitoring disease progression during treatment.
Validation in clinical practice
Most data so far come from research studies. Rigorous validation in clinical practice and diverse populations will be important as blood tests transition to widespread real world use.
Could Alzheimer’s blood tests lead to new treatments?
If blood tests enable earlier Alzheimer’s detection, this could open new opportunities for developing and applying treatments to slow or prevent decline in high risk individuals. Possible impacts include:
Screening for clinical trials
Blood biomarkers could improve enrollment efficiency for Alzheimer’s drug trials by allowing screening of many more asymptomatic candidates with preclinical disease.
Monitor drug effects
Quantifiable blood biomarkers could help assess effectiveness of new therapies in trials and optimize dosing regimens.
Identify candidates for treatment
Blood tests may identify individuals with early Alzheimer’s pathology who could benefit most from starting preventive therapy before extensive brain damage occurs.
Develop precision medicines
Biomarker profiling could enable personalized medicine approaches tailoring Alzheimer’s treatment based on an individual’s specific disease characteristics.
Accelerate novel therapies
Earlier diagnosis and precise monitoring could accelerate development of emerging Alzheimer’s treatments like immunotherapy and genetic therapies.
Widespread access to minimally invasive, low cost and accurate Alzheimer’s disease blood screening could transform efforts to develop disease modifying or preventive therapies. This could ultimately shift Alzheimer’s from an untreatable to a treatable condition. Realizing this potential will require rigorous validation of biomarker tests and continued research to maximize their power to detect Alzheimer’s pathology early.
Conclusion
In summary, developing accurate and non-invasive blood tests to detect onset and track progression of Alzheimer’s disease before symptoms manifest could be transformative for clinical care and therapeutic research. While still in experimental phases, current Alzheimer’s blood biomarkers like amyloid beta, tau and other proteins show promising performance for detecting early Alzheimer’s pathology in studies. These blood tests could eventually enable screening broad populations, catching the disease earlier in high risk individuals and accelerate development of novel Alzheimer’s treatments. However, challenges remain in optimizing sensitivity, especially for preclinical disease stages, and rigorous validation in clinical practice is still needed. Overall, Alzheimer’s blood tests hold exciting potential but require ongoing refinement, validation and integration with other diagnostic modalities to realize their full impact. Widespread accessible blood screening could be a game-changer in tackling the growing Alzheimer’s disease epidemic.
