The Science
Video: How Alzheimer's Changes the Brain
The scientific community’s understanding of the pathological processes defining Alzheimer’s disease, namely the formation of beta-amyloid plaques and hyper-phosphorylated tau tangles, is currently experiencing a rapid and welcome transformation due to the advent of easily accessible blood-based biological markers of disease (biomarkers). The capability to effectively measure biomarkers across all stages of Alzheimer’s disease provides new opportunities for both the clinician and patient to enable greater well-being, planning and preparation throughout the disease continuum.
An understanding of the science behind these advances can help people take control of their journey and create hope for today.
Diving into the science
Alzheimer’s disease (AD) is associated with protein abnormalities in brain cells resulting in the formation of the two pathological hallmarks of the disease: amyloid plaques and tau tangles. Amyloid plaques are toxic to nerve cells and can form in the brain because of abnormal activity of a protein called the amyloid precursor protein. AD-related biochemical changes to tau protein (hyperphosphorylation) cause dysfunction and aggregation of the tau protein into tangles. The accumulation of tau tangles within the nerve cell impedes the transport of essential nutrients, inhibiting nerve cell function, leading to cell death.
Specialized testing, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and spinal fluid analysis, are currently used to assess these and other Alzheimer’s related brain abnormalities and can be useful in suggesting the possibility or probability of AD. However, none of these tests are completely definitive nor stand-alone tests.
The revolution of blood-based biomarkers
Compared to current methods for determining the likelihood of AD, blood-based biomarker tests are less expensive, less invasive, and are more broadly accessible because they do not require highly specialized instruments. In particular, pTau217 is a tau protein found in blood that is considered to have the highest accuracy in predicting a diagnosis of AD. This is supported by longitudinal studies where pTau217 predicted future progression from normal cognition and mild cognitive impairment to AD and in post-mortem studies where pTau217 differentiated AD from other types of dementia.
ALZpath has established a robust and scalable plasma-based ultra-sensitive assay, branded ALZpathDx, utilizing a proprietary monoclonal pTau217 antibody and peptide calibrator. This ultra-sensitive blood-based ELISA assay has been developed on the semi-automated single-molecule array Simoa® platform. ALZpathDx has been launched for clinical use as laboratory-developed test (LDT). Evaluation in independent clinical cohorts with multiple co-morbidities is currently being established to advance to an in-vitro diagnostic (IVD). This pTau217 Simoa® assay is a fit-for-purpose validated assay now available for commercial use.
The introduction and widespread use of accurate and universally available blood-based biomarkers will revolutionize early diagnosis. It will enable doctors, patients and their families to make more informed decisions much earlier in the disease process.
The evolution of an Alzheimer’s disease diagnosis
For clinicians, cognitive testing has been the foundation of AD diagnosis for the last 45 years. However, cognitive testing alone has proven to be inaccurate, particularly in the early stages of the disease. Indeed, preceding the early 2000’s, autopsy after death was the only definitive way to know if a patient had AD. Thankfully, during the last 20 years, brain imaging analyses such as PET, CT, and MRI have developed to assist in diagnosing AD with more confidence. However, brain scans, particularly the cornerstone amyloid PET scanning, are expensive, expose participants to radiation, and are inaccessible for many patients. These shortcomings compromise the usefulness of these procedures for both patients and clinicians.
Over the last decade, the development and availability of cerebrospinal fluid (CSF) biomarker assessments to investigate pathological changes in AD has become a significant supplementary procedure to bioimaging. Monitoring CSF for amyloid plaque-related and tau proteins reflect biochemical changes along the AD continuum, becoming an important complementary diagnostic tool in clinical practice. Notwithstanding the clinical utility of CSF, sample procurement (lumbar puncture) is an invasive medical procedure requiring specialist practitioners in a hospital setting.
Alois Alzheimer publicly presents his finding on pre-senile dementia on November 3rd, 1906 at the Tübingen meeting of German Psychiatrists. In 1907 Alois published a scientific manuscript detailing his research about the disease. By 1910 the disease became known as Alzheimer’s Disease.
AD confirmed at autopsy with pathological diagnosis.
Brain imaging analysis such as PET, CT, and MRI developed to assist in diagnosing possible or probable AD.
Development and availability of cerebrospinal fluid (CSF) biomarker assessments to investigate pathological changes to assist in diagnosing possible or probable AD.
Blood-based biomarkers for phosphorylated tau demonstrate diagnostic accuracy and compare favorably with current corresponding CSF and neuroimaging biomarkers.
Plasma phospho-tau217 for demonstrates discriminative accuracy of Alzheimer’s disease vs. other neurodegenerative disorders with diagnostic precision equal to established diagnostic methods, including positron emission tomography (PET) imaging and cerebrospinal fluid biomarkers, both of which are expensive, invasive, and less accessible.
ALZpath is founded with the mission of transforming the Alzheimer’s disease ecosystem by innovating patient care, trials, and research through the integration of novel blood-based biomarkers, cognitive assessment tools, and care solutions.
The science behind the PathFinder
As the science of Alzheimer’s disease (AD) has evolved over the years, so has the way in which we diagnose and care for individuals with AD.
Our PathFinder team of dementia experts provide navigation and management of the Alzheimer’s disease journey. We shape meaningful conversations with individuals and their families about diagnosis, prognosis, treatment, education and support options as well as information on research, clinical trials and emerging therapies.
Studies consistently demonstrate that people living with Alzheimer’s disease who receive ongoing support, education, and guidance from trained Alzheimer’s disease professionals, have improved quality of life and are more likely to avoid visits to the emergency department and hospital.
As the science continues to evolve, we’ll continue to provide pathways to a better life.
Publications of Interest
Analytical and Clinical Assessment of Plasma Phospho-Tau Isoforms in Alzheimer's Disease (AD)
Neurology, 2023
Biofluid-based biomarkers for Alzheimer's disease-related pathologies: An update and synthesis of the literature
Alzheimer’s and Dementia, 2022
Moving fluid biomarkers for Alzheimer's disease from research tools to routine clinical diagnostics
Molecular Neurodegeneration, 2021
The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers
European Journal of Nuclear Medicine and Molecular Imaging, 2021
