Tauopathy’s Role in Aβ Oligomer Formation: New Insights from Transgenic Primate Models on Alzheimer’s Pathogenesis

Tauopathy, characterized by protein tau and Aβ oligomer accumulation, is a significant aspect of Alzheimer’s disease. The causal relationship between these accumulations and neurodegeneration remains unclear despite their links to various cognitive and movement disorders. A recent study1, published in Signal Transduction and Targeted Therapy, employed transgenic cynomolgus monkey models, expressing Tau (P301L) through lentiviral infection, leading to age-dependent neurodegeneration and motor dysfunction in these primates. Researchers used stereotaxic injections to introduce Tau (P301L) via AAV9 infection, produced at PackGene Biotech, into adult monkey and mouse brains. Remarkably, tauopathy, following embryonic transgenic Tau expression or brain injections of AAV-Tau, spurred the creation of Aβ oligomers in the monkey spinal cord, contributing to neurodegeneration. However, such Aβ oligomer generation was absent in other brain regions of transgenic Tau monkeys and in the mouse brains, indicating a species- and brain region-dependent phenomenon.

The findings were groundbreaking as they depicted, for the first time, that tauopathy could trigger Aβ pathology in primate spinal cords, shedding light on the pathogenesis and potential treatment avenues for tauopathy. While rodents have historically offered insights into tauopathy, the significant biological differences between rodents and humans pose limitations, marking primates as more relevant models for such studies. This particular study capitalized on this advantage to uncover that mutant Tau induces not only neurodegeneration but also Aβ oligomer formation, establishing a new understanding of Tau’s role in Alzheimer’s pathogenesis.

Furthermore, the study spotlighted motor dysfunction in monkey models, which mirrors symptoms in some human tauopathy-associated diseases. The emergence of Aβ oligomers specifically in the monkey spinal cord demands further investigation, hinting at the spinal cord as a possible initial site for Aβ accumulation in humans. Overall, this study underscores the potential of targeting Tau-induced Aβ formations for therapeutic strategies, emphasizing the significance of spinal cord investigations in tauopathy research.

Expression of Tau through AAV recreated the formation of Aβ oligomers in the monkey spinal cord, providing insights into tauopathy research. At PackGene Biotech, our relentless commitment to refining AAV production ensures top-quality AAVs throughout the research to clinical stages. Leveraging our vast expertise, we are dedicated to bolstering your efforts in developing groundbreaking treatments.

1. Tauopathy promotes spinal cord-dependent production of toxic amyloid-beta in transgenic monkeys. Tu Z, Yan S, Han B, Li C, Liang W, Lin Y, Ding Y, Wei H, Wang L, Xu H, Ye J, Li B, Li S, Li XJ. Signal Transduct Target Ther. 2023 Sep 22;8(1):358. doi: 10.1038/s41392-023-01601-6. PMID: 37735155; PMCID: PMC10514290.