An in vitro assay of human hippocampal neurogenesis (HN) which utilises an established human hippocampal progenitor cell line and patients’ human serum to provide prediction of progression from mild cognitive impairment (MCI) to Alzheimer’s Disease (AD) and helps distinguish those individuals diagnosed with MCI who will or will not develop AD.
Technology Overview
Dementia due to AD is preceded by a long preclinical stage, followed by diagnosis of MCI and not everyone diagnosed with MCI will develop AD. It is generally agreed that any putative disease-modifying therapies would be most beneficial if administered before the clinical onset of dementia or during the preclinical stage. Therefore, without refining diagnosis of individuals with MCI at risk of conversion to AD, it remains impossible to correctly target pharmacological and lifestyle interventions aiming at preventing or delaying the onset of clinical symptoms of dementia and preserving functional independence.
King’s researchers have utilised an established human hippocampal progenitor cell line and longitudinal serum samples from MCI patients who either converted to AD (MCI converters) or remained cognitively stable over consecutive follow-up visits (MCI non-converters), to establish the contribution of the human systemic
environment (serum) to the fate of hippocampal progenitor cells.
This has led to the development of a predictive model to estimate conversion probability from MCI to AD for individuals with MCI.
They have demonstrated that the systemic environment significantly impacts on hippocampal progenitor cells during progression from MCI to AD and that conversion to AD is associated with changes in average cell count, proliferation, cell death and neurogenesis. MCI converters can be distinguished from MCI non-converters using markers of proliferation, neurogenesis and cell death.
The prediction model (AUC=0.9675) indicates an excellent discriminative performance of the model. Sensitivity = 92.11%, Specificity = 94.12%, Positive predictive value = 97.22%, Negative predictive value = 84.21%. Furthermore, prediction can be made up to 3.5 years before AD diagnosis allowing time for intervention, a key strength of this assay.
Benefits
This in-vitro cell based assay can be used for:
• Monitoring disease progression from MCI to AD in a patient diagnosed with MCI
• Stratification of patients who have received a diagnosis of MCI for suitability for inclusion in an AD drug clinical trial
• Assessment of the efficacy of a therapy administered to a patient diagnosed with MCI
Development status
This assay has so far been established in small longitudinal cohorts over 6 years follow-up (MCI converters, n=38), (MCI non-converters, n=18) and validated via machine-learning. Further assay development and validation work is ongoing in Dr Thuret’s lab.
Opportunity
King’s College London is seeking a partner and funding for further assay development and validation activities. The UK priority application claiming this assay is available for licensing.