Alzheimer’s Disease: Cellular Origins and Reelin Effects

This project aims to elucidate the major molecular factors causing early AD pathology by developping a new type of human neuron-specific culture protocol.

Molecular Neurosciences
Alzheimer’s Disease
Cell Culture
Began Around

February 5, 2024


AD is the most common neurodegenerative disease leading to dementia, and its increasing prevalence is placing an ever-increasing burden on healthcare systems worldwide. Current AD treatments merely alleviate some symptoms, but as the root cause has remained elusive, no cure has been found yet. Developing such a treatment or cure will undoubtedly require a much deeper understanding of the initiating events of the AD cascade. This is the goal of this project. The initiation of AD is tied to intraneuronal accumulation of Amyloid-β (Aβ) oligomers and neurofibrillary tangles (NFTs), leading to massive neuronal degeneration. All this typically starts in a specific population of neurons, that express a protein called reelin, and which are located in the lateral entorhinal cortex (LEC) layer II (LII). However, the reasons for this specificity remain poorly understood. This is largely because current models fail to replicate the early spatio-temporal dynamics of AD, preventing us from unraveling the underlying causes. To bridge this gap, AD-CORE will generate human subject-specific reelin-expressing LECLII-like neurons, which will allow me to manipulate key neuron-specific proteins, and study crucial molecular mechanisms underpinning the onset of the disease.

This project is funded by a research grant from Nasjonalforeningen for Folkehelsen