Advancements in early detection and innovative therapies targeting tau pathology

Alzheimer’s disease (AD) robs millions of individuals of their memories, cognitive function, and independence, placing an immense emotional and financial burden on families and healthcare systems worldwide.¹ Characterised by the abnormal accumulation of two proteins, amyloid beta and phosphorylated tau (pTau), AD progresses insidiously, with patients living with the disease for many years before showing any symptoms.²

Due to the lack of understanding of AD’s definitive cause and associated biomarkers, clinicians rely on complex, correlative methods to determine disease progression. They perform invasive tests, such as lumbar punctures, to analyse cerebrospinal fluid (CSF) or costly positron emission tomography (PET) brain scans. These methods are only useful in identifying the disease once symptoms have progressed to higher stages, leading to a diagnosis that comes too late and deprives patients of the benefits of early intervention.³

With limited options for patients with AD, there is a critical need to advance novel therapies that may halt or reverse disease progression. To do so will require better diagnostic tools, such as blood-based tests, that can identify patients earlier, before the onset of cognitive decline.⁴ These tests may improve clinical trial patient recruitment and therapy evaluation, increasing the likelihood of developing successful disease-modifying treatments. They also have the potential for being more accessible and cost-effective than CSF analysis and PET scans.⁵

Blood-based p217tau assay: A breakthrough in early detection

Compared to traditional AD diagnosis methods, blood tests can be minimally invasive, cost-effective, and more accessible.³ Research has demonstrated that biochemical changes can be detected up to 20 years before the onset of symptoms, and one of these changes is the hyperphosphorylation of the tau protein.⁴ This is thought to lead to the aggregation and spread of tau tangles through the brain.⁵ With approximately 30% of proteins in eukaryotic cells being subject to phosphorylation, it is critical to select a precise epitope to measure.⁶ Differently phosphorylated fragments of tau can be detected in the blood, but previous assays were not sensitive enough to measure changes in the earliest stages of disease.⁷

Researchers are now focused on testing for a promising blood-based biomarker, p217tau. Plasma p217tau appears in early stages of AD and shows a strong correlation with amyloid deposits, tau tangles, cognitive decline, and brain atrophy. Tests that identify the presence of p217tau in blood plasma can detect amyloid pathology with over 90% accuracy, meeting revised criteria for diagnostic biomarkers, published by the Alzheimer’s Association in light of the latest science and test capabilities.^8,9 P217tau has emerged as a top performing biomarker for AD, enabling clinical sensitivity and specificity in blood,¹⁰ with a cohort of p217tau assays outperforming other leading assays for detecting amyloid pathology.¹¹ Large-scale trials have also demonstrated that the use of a p217tau assay as a pre-screening tool increased the efficiency of identifying suitable candidates for trials.¹²

At J&J, we are integrating our proprietary assay that measures p217tau levels to our clinical research. Studies have demonstrated that the assay is highly sensitive and can predict patients’ AD status with 91% accuracy.¹³

The FDA’s recent breakthrough designations and approvals of AD blood-based tests for clinical research highlight the critical need and appetite for non-invasive testing methods that can aid in AD diagnosis and improve patient enrolment in clinical trials.¹⁴ With several assays to measure tau pathology available, we are also one step closer to integrating blood-based biomarkers into routine clinical practice, and not just clinical trials.

Addressing an urgent global need: From diagnosis to effective treatments

The global burden of AD is staggering, with an estimated 55 million people worldwide living with the disease. While advancements in diagnostics are helping enable early identification of patients at risk of AD, there remains a critical need for effective therapeutic solutions to halt or potentially reverse disease progression.¹⁵ Supported by the power of early detection, various innovative therapies are in development to provide solutions for patients identified with elevated tau levels or at risk of AD. Over the past couple of years, we have seen disease-modifying therapies for AD approved by the US FDA, with many others in development.¹⁶

One key development is monoclonal antibody targeting of p217tau, which is being investigated for early AD treatment. Ongoing studies are examining whether it can slow the spread of tau pathology and the progression of AD symptoms. For example, in collaboration with AC Immune, J&J is also exploring active immunotherapy to potentially induce the body to produce antibodies against pathological tau and ultimately prevent disease progression in preclinical patients who have no cognitive symptoms.

The ripple effect of early detection

The promise of blood-based tests and biomarkers like p217tau represents a transformative advancement in AD diagnosis and treatment. By identifying AD pathology before cognitive decline begins, we can improve clinical trials, intervene earlier, possibly slow disease progression, and enhance the quality of life for millions of individuals affected by this devastating condition.¹⁷