Cologne researchers discover key proteins for Alzheimer's therapies!

Cologne researchers discover key proteins for Alzheimer's therapies!

Scientists at the University of Cologne have identified a special form of tau protein that plays a crucial role in the toxicity of protein clumps in human neurons. This research was led by Dr. med. Dr. rer. nat. Hans Zempel at the Institute for Human Genetics and the Center for Molecular Medicine Cologne (ZMMK). The results were published in the scientific journalAlzheimer's & Dementiapublished. This is the tau isoform 1N4R, which has been shown to mediate the toxic effects of protein clumps in human brain cells, such as uni-koeln.de reported.

The study used human induced pluripotent stem cells (iPSCs), which are derived from other cells such as skin cells and then reprogrammed into brain cells. Using state-of-the-art techniques such as CRISPR/Cas9 and live cell imaging, the research team was able to express different forms of the tau protein in nerve cells and analyze their effects. Dr. rer. nat. Sarah Buchholz, the study's lead author, highlights the progress in understanding Alzheimer's disease and highlights the importance of 1N4R-Tau as a potential target for future treatments. The interdisciplinary approach that the scientists took advances the understanding of Alzheimer's disease and shows the relevance of human cell models in research.

Neurodegenerative diseases and tauopathies

The identification of the tau isoform 1N4R is particularly relevant given that imbalances in the ratio of tau isoforms can lead to neurodegenerative diseases. According to scientific analysis, studies show that tauopathies are characterized by intracellular aggregates of hyperphosphorylated tau and are associated with an extensive neurodegenerative process. Tau is considered an important driver of neurodegeneration in certain tauopathies, however the specific contribution of the different isoforms to neuronal functions and disease development remains largely unclear pubmed.ncbi.nlm.nih.gov describes.

Overall, an estimated 57 million people worldwide suffer from dementia, with Alzheimer's disease (AD) alone contributing to 60-70 percent of cases. The number of AD cases in the US increased to 6.5 million from 5.4 million in 2018. These figures highlight the significant financial burden associated with Alzheimer's disease on both caregivers and the healthcare system pmc.ncbi.nlm.nih.gov.

Research and future therapies

Previous therapies focused primarily on amyloid beta (Aβ) but were largely ineffective. Only therapeutic approaches such as lecanemab and donanemab have shown a moderate slowing of cognitive decline in phase III studies. Current research efforts are increasingly focused on the tau protein, whose pathology correlates better with dementia severity than Aβ.

Tau pathology includes phosphorylated tau, pre-tangles, and neurofibrillary tangles, providing several potential targets for intervention. As the disease progresses, the challenges posed by ineffective tau-based therapies cannot be overlooked. The development of specific targeting strategies that address both intracellular and extracellular forms of tau is considered necessary to optimize therapeutic approaches.

Clinical research focuses on various approaches to treating tauopathies, including immunotherapies, antisense oligonucleotides, tau aggregation inhibitors, and microtubule stabilizers. The next steps in this important research direction are a much-needed validation of the results of the basic studies and the development of effective therapeutics.