New Biomarkers for Better Neurodegenerative Disease Diagnostics and Treatments

Neurodegenerative diseases place a devastating burden of disability and mortality on people worldwide, affecting roughly 15 percent of the global population. This category encompasses a diverse range of conditions characterized by progressive decline of nervous system function, including Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, amyotrophic lateral sclerosis, or ALS, and more. 

Despite the high prevalence of neurodegenerative diseases, progress in therapeutic development has been limited. No curative treatments are currently available for any neurodegenerative disease, and the often-overlapping symptoms and pathologies of these conditions can make accurate diagnosis challenging. 

Improving clinical trials for neurodegenerative diseases

Nearly 3,000 neurodegenerative disease clinical trials are currently underway, but we can only conduct scientifically sound clinical trials when we know we’re selecting the right patient population. This robust development landscape has further highlighted the need for improved diagnostics to improve clinical trials and usher groundbreaking therapies to approval. 

Accurate, sensitive, and specific diagnostic tools help to identify patients with consistent disease characteristics, reducing variability among clinical trial participants and making treatment effects more clearly detectable. 

Additionally, molecular diagnostics that enable early disease detection are particularly vital for neurodegenerative disease trials. Patients recruited to studies in earlier stages may benefit more from interventions designed to slow disease progression. 

Many neurodegenerative diseases are not diagnosed until cognitive or motor symptoms emerge, by which time significant and irreversible deterioration has often occurred in one or more brain regions. For example, approximately 30 percent of dopaminergic neurons within the substantia nigra are already lost by the time by the time motor symptoms of Parkinson’s disease are first observed. Molecular biomarker tests that reflect the underlying biology of a disease are thus vital for early and accurate diagnosis and intervention. 

New reliable biomarkers

Fortunately, a growing number of specific and reliable neurodegenerative disease biomarkers have been identified to meet this need, with several tests currently approved and numerous others in development. 

Changes in cerebrospinal fluid (CSF) biomarkers, including p-Tau217, p-Tau181, amyloid-β, ɑ-synuclein (ɑ-Syn), and neurofilament light chain, are detectable from the earliest stages of Alzheimer’s disease. Assessments of these markers at early stages can support more specific and accurate diagnosis than clinical evaluation alone. 

While novel blood-based tests have also entered the landscape, biomarker concentrations in blood are often lower than those of CSF, limiting the widespread applicability of such assays thus far. In addition, some blood-based biomarkers may also detect disease processes occurring outside of the central nervous system, making it challenging to track pathology specific to the brain.

Complex cases have multiple corresponding biomarkers

Several neurodegenerative diseases share common biomarkers in addition to overlapping symptoms. 

For example, Parkinson’s disease, Lewy body dementia, and Alzheimer’s disease with Lewy body pathology are all characterized by misfolded ɑ-Syn aggregates in CSF and Lewy Body Pathology in the brain, but clinical distinction of synucleinopathies from other neurodegenerative conditions is often error-prone. ɑ-Syn seed amplification assays, such as Amprion’s SAAmplify, enable accurate molecular diagnosis of synucleinopathies with over 95 percent accuracy and can be combined in panels with additional biomarkers for greater specificity. 

Since many of the common neurodegenerative diseases have recently been shown to have multiple co-pathologies (e.g., amyloid plus tau plus synuclein in up to 40 percent of Alzheimer’s patients), these more complex cases may also show multiple corresponding biomarkers that can aid in both diagnosis and treatment.

Driving therapeutic innovation

Sensitive and specific neurodegenerative biomarker tests are not only necessary to provide clarity to patients and their families but also vital in driving therapeutic innovation. 

Early and accurate diagnosis of these conditions empowers efficient and scientifically sound clinical trials, accelerating the path of desperately needed therapies through development and approval. 

Intervening in neurodegenerative disease progression is a race against time, but diagnostic tools that provide a clearer view into disease pathology can help fuel the development of potentially lifesaving therapies.