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New Blood Test for Alzheimer's Diagnosis

September 2023

By: Cici Zhu


When it comes to Alzheimer’s disease—a disorder that gradually impairs one’s memory and cognitive ability until they are no longer able to carry out simple everyday tasks—early diagnosis is crucial as it allows for the treatment and management of the disease’s progression. The diagnosis of Alzheimer’s is primarily accomplished using a combination of a patient’s medical history, neurological examinations, neural imaging, cognitive or functional evaluations, and cerebrospinal fluid (CSF) or blood tests. There is no one procedure that accurately determines whether a patient has Alzheimer’s, however, this may change with new research findings.


Throughout recent years, scientists have been exploring the development of biomarkers capable of detecting Alzheimer’s disease in a patient. One particular protein involved in the pathology of Alzheimer’s disease, tau (especially its phosphorylated version p-tau), has been the focus of Alzheimer’s research efforts. The tau protein is responsible for stabilizing neurons’ internal skeletons—tube-shaped vessels through which essential substances such as nutrients are transported throughout the neuron. In a patient afflicted with Alzheimer’s, a buildup of an abnormal form of tau causes the internal skeletons of the neurons to fall apart. The abnormal tau proteins can then cling to other tau proteins within the neuron, leading to the formation of tau tangles. This is a significant indicator of Alzheimer’s, and as such, this protein holds potential for the diagnosis of this disease.



A new blood test for p-tau biomarkers show promising results when used to test for Alzheimer’s in patients with early symptoms such as memory issues, although the blood test alone is not enough as a diagnosis tool for the disorder. A misdiagnosis poses significant consequences including high costs and medical risks, as well as ethical and psychological considerations. However, when it is used as part of a two-step procedure, the accuracy rate of diagnosis becomes much higher.


The first step is a diagnostic model which takes the p-tau217 test into consideration along with age and APOE e4—the e4 allele of the Apolipoprotein E gene, one of the most significant genetic risk factors for Alzheimer’s. The model scans patients with mild cognitive impairment (MCI) for risk of positive amyloid PET (an imaging method that uses radiopharmaceuticals to detect amyloid in the brain) results, which would suggest a neurological disorder such as Alzheimer’s. For patients with uncertain results in step one, CSF Ab42/40 ratio tests or amyloid EPTs are then performed. Ab42/40 refers to the ratio of Beta amyloid 42 (the beta amyloid variant most commonly found in CSF) to Beta amyloid 40 (found in senile plaques); a decreased ratio strongly indicates Alzheimer’s.


Finally, these results are used to classify patients as having either a low, intermediate, or high risk of Alzheimer’s. This workflow was shown to yield exceptionally high accuracy, with as few as 6.6% false negatives and 2.3% false positives found in an evaluation with 348 participants with MCI. This work was presented by researchers at the University of Gothenburg and the University of Lund, and it provides significant new possibilities for early diagnosis of Alzheimer’s disease. Those who are classified as high-risk by the two-step workflow can be diagnosed with high accuracy and be given symptomatic treatments, and Alzheimer’s can be excluded as a possibility with high certainty for those who are classified as low-risk.


References

 

Alzheimer’s Association. (n.d.). Medical Tests for Diagnosing Alzheimer's. https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests


Centers for Medicare & Medicaid Services. (2023, August 4). Amyloid PET. https://www.cms.gov/medicare/coverage/coverage-with-evidence-development/amyloid-pet


Chapleau, M., Iaccarino, L., Soleimani-Meigooni, D., Rabinovici, G.D. (2022). The Role of Amyloid PET in Imaging Neurodegenerative Disorders: A Review.


Gharbi-Meliani, A., Dugravot, A., Sabia, S. et al. (2021, January 4). The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study. https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00740-0


National Institute on Aging. (2021, March 16). Study reveals how APOE4 gene may increase risk for dementia. https://www.nia.nih.gov/news/study-reveals-how-apoe4-gene-may-increase-risk-dementia


National Institute on Aging. (2023, April 5). Alzheimer's Disease Fact Sheet. https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet



University of Gothenburg. (2023, August 31). New blood test gives very high accuracy to screen for Alzheimer's disease. https://www.sciencedaily.com/releases/2023/08/230831121807.htm


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