Longer life expectancy and ageing populations will lead to an increase in the prevalence of Alzheimer's Disease across the globe. However, symptoms can be vague and non-specific, hindering diagnosis. The most effective treatments should be administered early in the progression of the disease. How can clinicians ascertain a diagnosis more quickly and accurately? Blood biomarker testing might provide the answer. By Andjela Obradovic
Alzheimer’s disease (AD) is the most common form of dementia, with 1 in 5 women and 1 in 10 men developing AD during their lifetime (Palmqvist et al., 2024). There are currently 75 million people living with dementia globally, with that number projected to increase to 130 million by 2050 (Hansson, 2021). A neurodegenerative disorder characterized by a variety of clinical manifestations, AD usually starts with mild memory symptoms and progresses insidiously towards deficits in other cognitive functions, such as spatial and temporal orientation, language and judgment impairment, behavioural changes and mood swings. There is currently no cure for AD, although there are many pharmacological treatments that slow down disease progression. However, these treatments require an accurate and timely diagnosis to be effective, which can prove difficult.
Unfortunately, there is a significant delay in AD diagnosis, due to unspecific or mild symptoms at the onset of disease which can be mistaken for other conditions. AD is misdiagnosed in 25-35% of patients treated in specialized clinics (Hansson, 2021). Insights into the pathophysiological mechanisms of the disease have helped researchers discover AD-associated molecules in the brain which can be measured using medical tests. These molecules are known as biomarkers.
In the context of AD, diagnostic biomarkers can be routinely detected to using positron emission tomography (PET) scans and cerebrospinal fluid (CSF) samples (Ashton and Zetterberg, 2025). These measures are useful and necessary for stratifying patients that are eligible for AD immunotherapies, as well as following disease progression. However, these methods are not always readily accessible -they can cause discomfort to the patient and expose them to harmful substances. This has prompted research into finding alternative ways to measure biomarkers, such as finding them in the blood. Thanks to advancements in diagnostic assays such as mass spectrometry and increased research into AD pathology, several blood biomarkers have been identified in the past 10 years.
AD is characterised by the accumulation of neuritic plaques of amyloid-β (Aβ) protein in the grey matter of the brain, but also the formation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau-protein – an insoluble microtubule-associated protein (Hansson, 2021). The phosphorylated tau-protein (p-tau) has neurotoxic effects which contribute to brain atrophy in AD. Aβ and p-tau are strong candidates for biomarker analysis. There are many variations of the proteins, among which p-tau217 has been reported to be more specific and can differentiate AD from other forms of dementia (Feizpour et al., 2024).
But how accurate is the use of blood biomarkers for AD diagnosis?
Researchers from Lund University, Sweden, have conducted a study investigating the accuracy of these biomarker tests in primary and secondary care facilities. During a four-year period, a group of 1213 diverse patients from different centres underwent clinical evaluation of their cognitive symptoms. Blood tests based on the ratio of plasma p-tau217 to non-p-tau217 combined with the ratio of Aβ 42 and Aβ 40 were used to identify AD and compared to standard protocols in primary care and specialist clinics (Palmqvist et al., 2024).
According to the reports, the biomarker tests showed an accuracy of 88-92% in diagnosing AD compared to a 73% and 61% accurate diagnosis by dementia specialists and primary care physicians, respectively (Palmqvist et al., 2024). This study validates the diagnostic performance of blood markers collected from a diverse cohort of patients with various comorbidities (Palmqvist et al., 2024).
It is challenging to identify AD in primary care, but the results of this study provide hope for improving identification of AD. This could not only improve identification of AD in primary care, but also help identify eligible candidates for new anti-amyloid treatments (Palmqvist et al., 2024). These blood biomarker tests outperform or are up to par with tests involving biomarkers found in CSF and by PET scan, which can help overcome the issue of accessibility across these diagnostic tools. It is important to note that these findings are yet to be evaluated in a clinical context (Palmqvist et al., 2024). AD can be asymptomatic for many years and cognitive symptoms are not unique to AD pathology. Therefore, correct interpretation of these results will be key.
Biomarkers can include molecules, as well as histologic, radiographic or physiological findings. They can be used to diagnose or monitor a disease, track response to therapy, predict outcomes, and indicate safety or risk (Califf, 2018). AD is one of many neurodegenerative diseases that could benefit from the implementation of biomarker discovery into diagnostic algorithms, prognostication and therapeutic development (See Figure 1). In the exciting era of precision medicine, biomarkers will play a crucial role in helping diagnose patients and finding potential targets for drug development.
Figure 1: Examples of biomarkers for neurodegenerative diseases (Hanson, 2021).
Reference list
Cover Image: Pexels: https://www.pexels.com/search/blood%20test/
ASHTON, N. J. & ZETTERBERG, H. 2025. A blood test for Alzheimer’s disease: a decade of progress and success. eBioMedicine, 112.
CALIFF, R. M. 2018. Biomarker definitions and their applications. Exp Biol Med (Maywood), 243, 213-221.
FEIZPOUR, A., DOECKE, J. D., DORé, V., KRISHNADAS, N., HUANG, K., BOURGEAT, P., LAWS, S. M., FOWLER, C., ROBERTSON, J., MACKINTOSH, L., AYTON, S., MARTINS, R., RAINEY-SMITH, S. R., TADDEI, K., WARD, L., STAGE, E., BANNON, A. W., MASTERS, C. L., FRIPP, J., VILLEMAGNE, V. L. & ROWE, C. C. 2024. Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform. eBioMedicine, 109.
HANSSON, O. 2021. Biomarkers for neurodegenerative diseases. Nature Medicine, 27, 954-963.
PALMQVIST, S., TIDEMAN, P., MATTSSON-CARLGREN, N., SCHINDLER, S. E., SMITH, R., OSSENKOPPELE, R., CALLING, S., WEST, T., MONANE, M., VERGHESE, P. B., BRAUNSTEIN, J. B., BLENNOW, K., JANELIDZE, S., STOMRUD, E., SALVADó, G. & HANSSON, O. 2024. Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care. JAMA, 332, 1245-1257.
