Nupur Kain

Ms Kain’s research will investigate the biochemical changes in the brain that preceed cognitive symptoms in people with Alzheimer’s disease. This research is based on her earlier study that showed a sharp decline in levels of a neurochemical called sphingosine 1-phosphate (S1P) in the hippocampus (the memory region) and temporal gyrus in the brain’s of people with Alzheimer’s disease. She will also look at the influence of a common genetic variation called APO-E4 on changes in these levels and the association with amyloid beta accumulation in brain tissue samples of people without Alzheimer’s disease. Future work will include determining the effect of S1P levels on cognitive function in mice with and without Alzheimer’s disease.

The main focus of my project is to investigate biochemical changes preceding cognitive dysfunction in the ageing human brain affected by Alzheimer’s disease. Recently I measured levels of the neuroprotective factor sphingosine 1-phosphate (S1P) that significantly declined in the hippocampus and temporal gyrus grey matter (GM) of human brain tissue (n=34) grouped according to the NIH-Reagan criteria for AD pathology than the control group. Currently I’m investigating the influence of APOE4 genotype inheritance on the effect of S1P and amyloid β (Aβ) load from 80 brain tissue samples with no AD pathology. Previously our lab group demonstrated lower S1P levels in samples with the APOE4 genotype than samples with the APOE3 and less common APOE2 genotype. Future work will include determining the effect of cognitive function in 12 month old sphingosine kinase 1 and 2 (SphK1 and SphK2 respectively) knockout mice with significantly lower levels of S1P than healthy controls. 

Aspects of memory will be assessed such as short term memory (Cheeseboard Paradigm) and recognition memory (Novel Object Recognition). Brains will then be removed for S1P quantification and determination of Aβ load to demonstrate the role of reduced S1P levels on cognitive function, which deteriorates during AD progression.

Ms Kain is a PhD candidate based at the Prince of Wales Clinical School, University of New South Wales.