Modeling Neurodegenerative Disorders: Where Are We Now?

January 26, 2026

Neurodegenerative diseases are chronic and progressive medical conditions that lead to neuronal degeneration and neuronal cell loss.¹ Their pathophysiology is complex and, depending on the affected brain region and neuronal types, they can present with a wide range of symptoms, affecting cognition, speech, motor function, balance, and vegetative function. Some of the neurodegenerative disorders with the highest public health impact include Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, and multiple sclerosis.

Age has been identified as the most important risk factor for many neurodegenerative diseases. Even though neurodegenerative diseases already are a leading cause of death and disability worldwide, as there is a demographic shift toward aging of the global population, their public health impact is expected to continue to rise.¹

Despite the existence of approved medications for neurodegenerative diseases, most of them ameliorate associated symptoms but cannot affect disease progression. Thus, there is an urgent need to gain further insight into the pathophysiology of neurodegenerative diseases and to develop novel and improved therapeutics. One of the approaches that can facilitate drug discovery is the use of disease models.

The Concept of Disease Modeling

The concept of disease modeling refers to the use of a cell or an animal to model pathological processes observed in a disorder affecting humans.² A disease model may occur naturally or may be induced experimentally. Depending on their design, there are three different types of disease models:

In vitro (cell-based) models – A variety of cell-based models can be used to study cellular and molecular mechanisms of disease. They may involve established cell lines, primary cell cultures, pluripotent stem cells, organoids, and microfluidic systems.
In vivo (animal) models – They represent integrated living systems, in which pathophysiological mechanisms, therapeutic targets, and the effects of experimental therapeutics can be examined. Examples of in vivo models include transgenic and lesion models.
Computational models – They rely on simulations and algorithms to gain insight into pathophysiological mechanisms of disease, predict disease progression, and identify novel therapeutic targets.

Why Disease Modeling of Neurodegenerative Diseases Matters

Factors that render research on neurodegenerative diseases particularly challenging are their complex pathophysiology and the inaccessibility of human brain tissue. The development and use of appropriate disease models is an important avenue to gain further insight into the pathophysiology of neurodegenerative diseases, to identify new therapeutic targets, and to investigate potential novel drugs.

In Vitro Disease Models of Neurodegenerative Diseases

A variety of in vitro models have been used in research on neurodegenerative diseases, including established cell lines, primary cell cultures, pluripotent stem cells, brain organoids, and microfluidic systems.

Established cell lines – Some of the immortalized cell lines most used in research on neurodegenerative diseases include: human neuroblastoma SH-SY5Y cells, human neuroblastoma SK-N-MC cells, and rat pheochromocytoma PC-12 cells. They enable high-throughput screening, can be obtained from commercial bioresource centers, and are relatively easy to handle. However, immortalized cell lines do not recapitulate all characteristics of primary cells and may undergo alterations in the process of cell culture.³ To more closely resemble the neuronal phenotype, immortalized cell lines can also be differentiated using established protocols.

Primary cell cultures – Primary neurons, astrocytes, and microglia can be isolated from rodent brains, cultured, and subjected to pharmacological treatments or molecular biological manipulations. Primary cell cultures enable the investigation of molecular pathways implicated in neuronal functions. However, their isolation and culture are more time-consuming, and interspecies differences may exist.

Pluripotent stem cells – These cell types have great proliferation capacity and the ability to differentiate into various cell types, including neurons, astrocytes, or microglia. They can be found in embryos (embryonic stem cells) or can be induced from somatic cells of individuals of different ages (induced pluripotent stem cells, iPSCs). iPSCs have contributed to advances in personalized medicine, since they retain the specific genetic characteristics of the individual from whom they were derived. In addition, researchers have generated numerous subtypes of human neurons from iPSCs, which can have important implications for drug development and testing.⁴ Importantly, stem cell transplantation holds great potential for the development of therapeutics for neurodegenerative diseases. However, most clinical trials are still in early phases, investigating the safety and preliminary efficacy of stem cell therapy.^5,6

Brain (cerebral) organoids – Cerebral organoids represent three-dimensional (3D) structures derived from human pluripotent stem cells. They encompass different cell types and have a complex architecture. Thus, they resemble parts of the human brain and enable research on cell-cell interactions and associated pathophysiological mechanisms.

Microfluidic systems – Also known as "organ-on-a-chip", these systems represent micro-engineered devices with integrated cells. They have advantages with respect to simulating brain regions or neurovascular units but are complex and technically challenging.

Challenges with Models of Neurodegenerative Diseases

Disease modeling of neurodegenerative disorders is also associated with challenges related to:

Brain complexity, which cannot be fully recapitulated with the use of a disease model.
Disease heterogeneity, with variability in the underlying pathophysiological mechanisms and clinical presentation of neurodegenerative diseases.
Ethical considerations, especially with regards to the use of animal models.

The Future Possibilities of Disease Modeling

Despite these challenges, disease models have played an important role in advancing the knowledge and understanding of neurodegenerative diseases and in facilitating the development of novel therapeutics.

Disease models can help to:

Accelerate drug testing by facilitating high-throughput screening.
Advance regenerative medicine by optimizing cell transplantation protocols.
Enable truly personalized, patient-specific therapies by using iPSCs, which retain the genetic characteristics of the individual they were derived from.

Bringing the Concept to Life

Disease models for neurodegenerative diseases promote the understanding of their pathophysiology, identification of novel therapeutic targets, and evaluation of therapeutic candidates. FUJIFILM Biosciences offers solutions that help scientists and innovators turn these possibilities into reality. We provide all necessary tools that scientists need to design patient-specific in vitro disease models. Including a wide array of antibodies suitable for investigation of neurodegenerative diseases, such as the microglial marker anti-Iba1 antibody, a trusted antibody that is cited in over 5,000 publications around the world.

Visit the Disease Modeling webpage for a closer look at our products and solutions. Stay tuned for the next article in this series, where we will explore more emerging trends in disease modeling. Subscribe to our mailing list for updates and follow us on LinkedIn to join the conversation.

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