Understanding Neurodegenerative Dementia

Definition and Types

Neurodegenerative dementia encompasses a range of neurodegenerative diseases characterized by dementia as the primary clinical symptom. Notable examples include Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Although individuals with Parkinson’s disease can also develop dementia, this occurs only when protein aggregations extend into the brain’s cerebral cortex.

Protein Accumulation in Neurodegenerative Diseases

Each of these diseases is marked by the accumulation of specific protein polymers in various brain cells. Alzheimer’s disease is associated with amyloid-β (Aβ) and tau proteins, while tau is the main protein implicated in frontotemporal dementia. In dementia with Lewy bodies, α-synuclein is the primary protein involved.

Current Treatment Landscape

As of now, there is neither a cure nor a reliable treatment for these neurodegenerative conditions, despite ongoing research from scientists and pharmaceutical companies. Many drugs aimed at treating these diseases have not demonstrated significant improvements in cognitive function during clinical trials. These trial failures are often attributed to two main factors: the late initiation of treatment and the selection of inappropriate drug targets.

Proposed Treatment Strategies

While a cure remains elusive, there is a growing consensus that earlier intervention may be beneficial—ideally before significant neurodegeneration occurs. Researchers suggest that future therapies should target oligomers, which are considered the fundamental building blocks of the insoluble polymers associated with these diseases.

Recent Preclinical Findings

A preclinical study conducted by scientists at Osaka City University Graduate School of Medicine explored the effects of a combination of an antibiotic (rifampicin) and an antioxidant (resveratrol) administered intranasally. This study was conducted using mouse models for Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies. The researchers identified the ‘pre-neurodegeneration’ stage for each model and initiated treatment one month prior to the onset of neurodegeneration.

After treatment, results indicated a notable reduction in toxic oligomers in the brains of the treated mice compared to control groups, alongside improvements in cognitive function.

Future Directions

Although this study represents a promising advance in the treatment of neurodegenerative dementia, the authors caution that it may take considerable time before this drug combination can progress to human clinical trials, as further testing is necessary. Despite the potential delay, this preclinical research lays a foundation for re-evaluating approaches to treat and possibly prevent neurodegenerative dementia.

Reference

Umeda T, Sakai A, Shigemori K, Yokota A, Kumagai T, and Tomiyama T. (2021) “Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination—A Preclinical Study in Model Mice” Frontiers in Neuroscience 15:763476 doi: 10.3389/fnins.2021.763476