New blood tests for Alzheimer’s disease predict pathological brain changes early
The diagnosis of Alzheimer’s disease (AD) has challenged neurologists for many years. It’s difficult to determine if someone will develop AD in the future, if the actual cognitive deficit is due to AD or to other cause of dementia and it’s also difficult to predict the pace or speed of disease progression.
It is already known that Alzheimer’s pathological brain alterations (amyloid plaques and Tau-tangles) start long time before the appearance of clinical symptoms. We also know that lifestyle interventions are the only effective treatment to fight cognitive decline, especially when initiated in early stages of disease. That’s why, a test which could predict when the process starts and the rhythm of progression would be a useful tool in the clinical practice.
Many tests are nowadays available (see Diagnosis section for more information), but they are expensive and difficult to be used in the day by day clinic. They usually require brain image techniques that are either expensive and time consuming or invasive medical procedure like lumbar puncture – which is not free of adverse effects.
Two new AD-tests have been developed within the last year and hope to finally bring ease and precision to the diagnosis of AD.
Published in Neurology in August 2019, a study presents a blood test that was able to measure the level of Aβ42/Aβ40 with high correspondence with amyloid PET status (brain image test). It showed that plasma Aβ42/Aβ40, especially when combined with age and ApoE4 status (see Genetics section for further information), accurately diagnoses brain amyloidosis and can be used to screen this pathological alteration in individuals with normal cognitive function, i.e., before presenting symptoms. It also showed that individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Thus, the test could be used to screen individuals likely to present brain amyloid deposit and hence, at risk for AD.
In another study published in Lancet Neurology in May 2020, the authors developed and validated an ultrasensitive blood immunoassay for p-tau181. Tau phosphorylated at threonine 181 (p-tau181) level has been already measured in is cerebral spinal fluid (CSF) and is a highly specific biomarker for Alzheimer’s disease pathology. With this study, the authors showed that blood p-tau181 levels can predict tau and amyloid β pathological alterations and differentiate AD from other neurodegenerative disorders with high accuracy. Additionally, it predicts cognitive decline and hippocampal atrophy over a period of 1 year, making it suitable as a marker of disease progression.
Both tests have the advantage to be done in a blood sample, and were able to predict the risk of developing cognitive decline and its progression. They represent simple, practical and scalable tests for the diagnosis of AD. They are not yet available in the market, but have the potential to be incorporated into clinical practice as a rapid screening test to rule out AD and to guide therapy in patients with dementia.
Considering the relevance of lifestyle measures for AD treatment and prevention, these tests provide security and certainty of when to start or intensify actions to control cognitive impairment. They can be also used to easily screen individuals at risk to future prevention trials, to promote lifestyle intervention and to improve our knowledge about this challenging disease.
Conclusion:
Two new tests for Alzheimer’s disease that determine highly specific biomarker substances in the blood, have been developed. These fast, precise and inexpensive tests may have important clinical applications: as a screening tool in the primary care setting; to monitor the disease progression; to differentiate AD patients from patients with other neurodegenerative disorders; and as a way of ensuring that subjects enrolled in clinical trials indeed have Alzheimer’s disease and that the treatments they are testing are effective. They will certainly become an important tool to ensure an accurate and early diagnosis and to motivate doctors and patients to implement lifestyle changes in order to prevent cognitive deterioration. KsD will keep its readers informed about the availability of these or other tests (please register today for our newsfeed).
References:
- Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19(5):422-433. doi:10.1016/S1474-4422(20)30071-5. https://pubmed.ncbi.nlm.nih.gov/32333900/
- Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647-e1659. doi:10.1212/WNL.0000000000008081 https://pubmed.ncbi.nlm.nih.gov/31371569/
