Alzheimer’s Disease is a degenerative neurologic disorder that results in the death of brain cells and atrophy or brain shrinkage. This illness is the most frequent cause of dementia, characterized by a steady deterioration in a person's behavioral, mental, and social abilities. In turn, this syndrome impairs the person’s capacity to function independently.

Need-To-Know Facts About Alzheimer’s

The Alzheimer’s Association estimates that 5.7 million Americans have the disease. This number is projected to grow to 13.8 million by 2050 without a medical treatment to prevent, slow, or cure the disease. Demographic trends show that it affects women more frequently than men.

The condition’s early symptoms include increasing bouts of forgetfulness. People with advanced Alzheimer’s will have severe memory loss and lose the skills to perform basic tasks as the condition worsens. Symptoms may momentarily get better with medication.

For patients identified as having early-stage Alzheimer’s, current FDA-approved treatments target cholinergic and/or glutamatergic neuronal function, which merely help manage the symptoms of the disease. However, there is no available treatment to stop or reverse the progression of the disease.

Alzheimer’s Disease is a complex broad-spectrum disease. A combination of genetic, environmental, and lifestyle factors contribute to the risk of developing Alzheimer’s Disease. Genetics play an important role in familial Alzheimer’s Disease (FAD), which has a typical onset before age 60 and is caused by mutations in three distinct genes. In sporadic Alzheimer’s Disease (SAD), which accounts for >95% of all cases, the age of onset is usually above 70, and there are several genes that increase the risk of developing the disease. Additionally, epidemiological data suggest that a history of traumatic brain injury (TBI) is a significant environmental risk factor in developing Alzheimer’s Disease.

Alzheimer’s Disease histopathologies can be grouped into four major categories: (1) Aβ plaques, (2) NFTs, (3) neuroinflammation, and (4) vascular dysfunction. The Aβ plaques are extracellular aggregates surrounded by atrophic neurites with a reduced number of synapses. The NFTs are intracellular tangles in pyramidal neurons. Neuroinflammatory responses, driven by activated microglia and astrocytes, are present in the early stages of Alzheimer’s Disease. Vascular dysfunction, caused by Aβ deposits in the capillaries leading to a chronic reduction in the supply of oxygen and nutrients to the brain, is detected in 90% of AD patients30. While the prevailing theory for AD pathogenesis hypothesizes that Aβ plaques, or species linked to them, contribute to the other downstream pathologies, we still have much to learn about the cause-and-effect relationships responsible for disease onset and progression.

In a Phase 3 clinical trial by Biogen and Eisai Co., the experimental drug lecanemab significantly slowed the progression of memory loss and other symptoms associated with the condition. Lecanemab targets the amyloid-β plaque buildup in the brain, which is linked to both Alzheimer’s and hypertension.

How Scientists Are Making Progress in Curing Alzheimer’s

With the potential exception of Lecanemab, hundreds of clinical trials over the past 30 years have failed to provide an effective treatment for Alzheimer’s Disease. A major obstacle to the development of effective treatments for this disease is the lack of suitable preclinical models for rapid testing of hypothesized mechanisms and screening of drug candidates. A high-throughput in vitro methodology is needed to (a) understand the disease pathologies of Alzheimer’s and their interactions, (b) understand how they relate to a history of traumatic brain injury and genetics, and (c) develop treatments that stop and reverse disease progression.

BMSEED was recently awarded a Fast Track SBIR grant from the National Institute of Aging (NIA) to develop a microfluidic chip-based platform for modeling Alzheimer’s disease and related dementias (AD/ADRD) for preclinical in vitro mechanistic studies and drug testing.

This grant aims to develop a novel microfluidics-based 3D in vitro AD model and merge this chip with BMSEED’s existing in vitro model platform for traumatic brain injury (TBI), the MicroElectrode Array Stretching Stimulating und Recording Equipment (MEASSuRE), a drug screening platform for neuroprotective compounds.

MEASSuRE presents an efficient and physiologically relevant pre-clinical drug screening platform for AD treatments. This platform is also well-suited to investigate the effects of a TBI on a person with or without a pre-existing genetic disposition to develop AD. The key innovations are the use of a stretchable microelectrode array in a 3D cell culture matrix for functional assessment of neuronal health in a microfluidics drug screening platform and the capability to investigate the mechanistic links and similarities between AD and TBI.

This 3D-MEASSuRE platform provides a more realistic in vitro facsimile of the natural in vivo biochemical and biomechanical microenvironment of the cells compared to existing 2D systems. Alzheimer’s researchers can get further updates on technological developments in neurodegenerative disease treatments through the BMSEED platform and stretchable microelectrode arrays.