EC‐03‐01: Reconstructing Alzheimer Amyloid and Tau Pathology in 3D Cell Cultures from Stem Cells
Year: 2016
Type: article
Abstract: Alzheimer’s disease (AD) affects 5.4 million individuals in the US with no effective therapeutic option available except for symptomatic treatments. Transgenic mouse models with FAD mutations have been used to study AD and for drug discovery. However, in these AD mouse models, deposition of beta-amylod does not lead to neurofibrillary tangle formation. Thus, there are profund limitations for their use as disease model. We previoulsy developed a novel 3D human neural cell culture model that recapitulates amyloid-β (Aβ) plaques and tangles (from endogenous tau) by expressing FAD mutations that lead to the deposition of beta-amyloid in roughly six weeks (Choi et al., Nature, 2014; Kim et al. Nature protocols, 2015). More recently, we have made 3D cultures using single-clonal human neural stem cells in a 96-well FACS-assisted single cell cloning protocol. These are being used for drug discovery aimed at preventing plaque and tangle formation. The clonal homogenous FAD cells secrete pathogenic Aβ species leading to plaques and phospho-tau/tangle pathology and exhibit dystrophic neurites, LDH release, and caspase 3 activation. They are currently being used for drug screening. The new single-clonal FAD cell lines, together with 3D culture technology, provide a novel model for studying AD neuropathogenesis and drug discovery.
Source: Alzheimer s & Dementia
Authors: Rudolph Tanzi, Doo Yeon Kim
Institutions: Harvard University, Massachusetts General Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2533840656