Stem cell lines to study familial Alzheimer’s disease

When many members are affected, genetic risk may be easier to detect

Medical experts studies the EEG condition of the patient

Dementia affects about 3.7 million people in India, which is 1% of population aged above 60. This number is set to increase as the population ages. There is a need to study Alzheimer’s disease more widely in the Indian context. A collaboration of scientists drawn from NIMHANS, NCBS and InSTEM has characterised two representative human-induced pluripotent stem cell lines (iPSC) from families with incidence of Alzheimer’s. The cell lines can now be used to further research into dementia and related disorders. The study was published in Stem Cell Research.

Preliminary data confirm that the lines mimic disease-relevant attributes which can used as proxy readout to understand disease mechanism in a dish, says Dr. Odity Mukherjee

 

Island of ignorance

“Neuro-psychiatric diseases represent a large ‘island of medical ignorance’. Shining a light on this area of darkness using all the tools available is essential,” says Dr. Sanjeev Jain of National Institute for Mental Health and Neurological Sciences, Bengaluru (NIMHANS), a member of this collaboration. “The lines generated have been deeply characterised, and preliminary data confirm that they mimic disease-relevant attributes which can be used as proxy readout to understand disease mechanism in a dish,” says Dr. Odity Mukherjee of Institute of Stem Biology and Regenerative Medicine (InStem), Bengaluru. The cohort from which the human iPSCs are drawn are well characterised: that is, the clinical symptoms, MRI studies, neuropsychology and family history for these subjects have been well documented. “So we are reasonably sure about the nature of the mutation that we have detected,” says Dr. Jain.

Genetic risk

This work is now extended as a part of the DBNS (Discovery Biology of Neuropsychiatric Syndromes) study which identifies and follows up many families who happen to have many members diagnosed with one or the other syndrome of psychiatric illness. When the disease affects many members in a family, the genetic risk is higher, and may thus be easier to detect.

“Identifying the shared genetics and then trying to understand how the genetic change translates itself into disease is the current work,” explains Dr Jain. “It’s a bit ambitious! But we are hopeful that with our clinical data, and scientific skills, we should be able to make some meaningful contribution,” he adds.