Alzheimer’s disease (AD) is a debilitating, complex, heterogeneous, and multifactorial neurodegenerative disorder that affects memory, thinking, and behavior, posing a substantial burden on patients, caregivers, and society. Traditional treatment approaches for Alzheimer’s have often fallen short, providing limited relief and no definitive cure. However, the advent of precision medicine offers a beacon of hope. By leveraging biomarkers, precision medicine aims to revolutionize Alzheimer’s disease treatment, promising more effective and personalized clinical practices.

As we explore the precision medicine approach to Alzheimer’s disease and the translation of biomarkers into clinical practice, it is timely to reflect on the topics to be presented and discussed at the upcoming Alzheimer’s Association International Conference (AAIC) 2024. Join the TFS HealthScience team at AAIC 2024 in Philadelphia, PA, from July 28-August 1. 

 

Alzheimer Disease Burden 

According to the World Health Organization (WHO), more than 55 million people are living with dementia worldwide, growing by nearly 10 million new cases each year. AD is the most common form of dementia, contributing to approximately 60–70% of cases. Due to the aging population, it is anticipated that the number of elderly with AD will quadruple by 2050 if effective interventions that prevent, stop, or slow disease progression are not developed. By 2050, the estimated number of patients with AD in the U.S. is 13.8 million. Despite its significant impact on individuals and health systems, there is no definitive antemortem diagnosis for AD pathogenesis, further exacerbating clinical research challenges.

Currently, available therapeutics have a negligible impact on the severity and progression of AD due to several factors; firstly, they are primarily symptomatic and do not address the underlying causes of AD. These treatments are not effective for all patients, have side effects, and may interact with other medications prescribed to the patient. Additionally, patients typically receive these treatments at a late stage when they have already suffered significant brain damage.  

 

Alzheimer’s Association International Conference (AAIC) 

The Alzheimer’s Association International Conference (AAIC) is the largest international conference on advancing dementia science and clinical practice. It brings together researchers, clinicians, and dementia professionals to share groundbreaking research discoveries and clinical practice education aimed at improving diagnosis, risk reduction, and treatment options for AD and other dementias. As the Alzheimer’s Association describes, every aspect of the field’s growing knowledge of dementia is incorporated into the world-class conference.  

 

Understanding Precision Medicine in Alzheimer’s 

The clinical presentation of AD is complex and rarely exists in isolation, as patients typically have other primary brain pathologies. The phenotype and progression of AD varies based on multiple factors, including the presence and severity of systemic comorbidities, genetic risk factors, and an individual’s cognitive reserve. Novel, cutting-edge methods and increasing knowledge of the complex causes of the disease are transforming AD research and treatment. At the forefront is precision medicine, where individualized treatment plans are based on genetic and biomarker profiles for customized therapeutics. Patients with AD would be categorized as specific patients or into patient subgroups based on clinical aspects, brain imaging, genetic profiling, clinical genetics, and epidemiological factors. Combination therapies being explored simultaneously attack Aβ plaques, tau tangles, neuroinflammation, and other factors.

Instead of a one-size-fits-all methodology, precision medicine in Alzheimer’s seeks to identify specific biomarkers that can predict disease progression, response to treatment, and potential side effects.

 

Structure & Function of γ -Secretases and Precision Medicine in Alzheimer’s

One of the featured research sessions at AAIC 2024 is entitled “Insights into the Structure and Function of Gamma-Secretases Lead to Precision Medicine in Alzheimer’s Disease.” Recent literature by De Strooper & Karran highlights two Phase III clinical trials with anti-amyloid peptide antibodies, which met their primary goal of slowing AD progression. They reviewed the structure, function, and pathobiology of gamma-secretases and proposed the term gamma-secretase allosteric stabilizers (GSAS) as compounds that stabilize the proteinase-substrate complex. De Strooper & Karran suggest that the GSAS represents a precision medicine approach as they specifically target a discrete aspect in a complex cell biological signaling mechanism that initiates the pathological processes that cause AD. 

 

Clinical Integration of Alzheimer’s Biomarkers

Biomarkers are biological indicators that can be measured to assess health conditions. In Alzheimer’s, common biomarkers include amyloid-beta plaques, tau proteins, and neuroinflammation markers detectable through various methods like cerebrospinal fluid analysis, blood tests, and advanced imaging techniques. These biomarkers provide crucial insights into the disease’s pathophysiology, enabling earlier and more accurate diagnoses.

The featured research session, “Strategies for Clinical Integration of Alzheimer’s Biomarkers,” will explore the translation of AD biomarkers into clinical practice. A recent overview of current biomarkers and treatment strategies in AD describes an ideal AD biomarker that would identify vital neuropathological characteristics, have a diagnostic sensitivity of over 80%, and have specificity for differentiating AD from other dementias above 80%. The value of an ideal biomarker makes it possible to accurately identify AD at its very early pre-clinical illness stage. Aβ peptides are among the most studied and important AD biomarkers. As changes in Aβ levels often precede symptoms, Aβ biomarkers are crucial for early AD detection and intervention. Aβ imaging, which uses positron emission tomography (PET) to visualize amyloid plaques in the brain, helps diagnose AD and track the progression of amyloid deposition. 

 

Clinical Biomarker Relevance of pT217-tau in Alzheimer’s Disease  

Another highlight from AAIC 2024 will be the featured research session “Emerging Neurobiology and Clinical Biomarker Relevance of pT217-tau in Alzheimer’s Disease.” Recent advancements have revealed pT217-tau or tau phosphorylated at threonine-217, a novel fluid-based biomarker in cerebrospinal fluid and blood plasma that appears in the earliest presymptomatic stages of AD and predicts the onset of AD symptoms. Research into AD has found that pT217‐tau reliably discriminates it from other neurodegenerative diseases, with high accuracy similar to cerebrospinal fluid‐ or PET‐based measures. In clinical trials, novel diagnostic biomarkers like pT217-tau will be vital for assessing the efficacy of novel interventions designed for early‐stage disease. 

 

Digital Biomarkers & Precision Medicine 

In the AAIC 2024 perspective sessions, digital biomarkers will be discussed. As AD can develop without noticeable symptoms and cause irreversible damage before signs are clinically evident, early detection methods are urgently required. A recent review explored digital biomarkers, or tools designed for remote neurocognitive data collection and analysis by artificial intelligence (AI), as a potential solution. It highlights studies that combine AI with digital biomarkers to identify pre-symptomatic indicators for neurodegenerative diseases, e.g., utilizing convolutional neural networks for eye tracking, which has demonstrated significant diagnostic accuracies. The authors conclude an urgent need to integrate validated digital health tools like digital biomarkers into mainstream clinical practice11. Another study assessed the value of digital biomarkers for AD and their potential role in precision medicine with the promise of faster, more precise, and personalized diagnosis.  

 

Combining Diet, Exercise, and Biomarker Insights 

One of the featured research sessions at AAIC 2024 will examine “Multidimensional Approaches in Cognitive Preservation: Combining Diet, Exercise, and Biomarker Insights.” A review of studies recently found that for studies incorporating inflammation biomarkers as an outcome, cross-sectional assessments consistently supported an association between higher diet scores and lower inflammatory markers. Studying the impact of diet and exercise on cognition and brain health in older adults, Key & Szabo-Reed (2023) highlight the many cross-sectional studies that consider nutrition’s anti-inflammatory/antioxidant benefits to explain why a diet is associated with better cognition. TFS recently shared insights on brain health and potentially modifiable lifestyle factors that improve cognitive functioning. 

 

Exercise for Prevention of Alzheimer’s Disease and Dementia: A Focus on Blood-Based Biomarkers 

Further on potential lifestyle changes, one of the AAIC 2024 perspective sessions will focus on “New Directions in Exercise for Prevention of Alzheimer’s Disease and Dementia: A Focus on Blood-Based Biomarkers.” Exercise is a promising preventive intervention for AD, associated with lower dementia risk, improved cognition, greater brain volume, and decreased brain beta-amyloid. A recent study examined the impact of exercise on blood-based biomarkers of AD in cognitively unimpaired older adults, specifically the influence of a 6-month exercise intervention on levels of plasma beta-amyloid, phosphorylated tau, glial fibrillary acidic protein, and neurofilament light chain, and whether blood-based biomarkers are related to cognition. The results highlighted the importance of body mass index (BMI) in analyzing blood-based biomarkers. More extended follow-up periods may be required to observe exercise-induced change in blood-based biomarkers. 

 

Progress Toward a Precision Medicine Approach For Alzheimer’s Disease 

Our last highlight is a featured research session addressing “The Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD) at 10: Progress Toward a Precision Medicine Approach for AD.” Launched in 2014, the AMP program is a public-private partnership between the National Institutes of Health, the U.S. Food and Drug Administration, non-profit organizations, and industry to transform the prevailing model for developing new diagnostics and treatments. The second iteration of the AMP program for AD (AMP AD 2.0) was launched in 2021 to enable a precision medicine approach to discovering novel targets and biomarkers through the transformative AMP partnership.  

 

Why TFS CRO in Neuroscience? 

Experience scientific and medical excellence in neuroscience. Our CRO team delivers all the scientific and medical aspects of your clinical program to help ensure market success. We support site start-up, patient access, referral, recruitment and retention, and investigator identification at global, regional, and local levels. With our internal experts and global network of key opinion leaders (KOLs), we ensure a comprehensive approach to your neuroscience and central nervous system (CNS) trials.

Join the TFS HealthScience team at AAIC 2024 in Philadelphia, PA, from July 28-August 1. Meet our seasoned team of neuroscience experts attending the conference to learn how to run accelerated clinical trials efficiently and effectively! 

 

TFS is Your Global CRO Partner in Neuroscience! 

TFS HealthScience is a global, mid-size contract research organization (CRO) headquartered in Sweden. TFS’s Neuroscience department provides full-service support to clients from early phase through Phase III, post-authorization, and real-world (RWE) studies. Our global operations teams are experienced in the unique challenges of neurology, psychiatry, CNS, and pain studies. We partner with clients to deliver tailored solutions that match their needs when and where they need them.

TFS has broad experience across a range of neuroscience indications and is present in over 3,000 sites. We have worked with more than 60 clients on over 335 trials in over 30 countries involving over 39,000 patients. Read more about TFS’s expertise in neuroscience. We have the right people and the right solutions to help you on your path to success.

Visit the TFS Neuroscience CRO website to learn more, or connect with a TFS representative here!