Dr Prashant Bharadwaj's innovative research and work is paving the way for new treatments and offering hope to families affected by dementia.
Combining his background in engineering and biotechnology with a passion for neuroscience, Dr Prashant Bharadwaj has identified a role for the PRKAG2[1] gene in Alzheimer’s disease. His research is providing a deeper understanding of amyloid buildup and potential ‘cleaning processes’ in the brain.
Dr Bharadwaj, from Edith Cowan University and Alzheimer’s Research Australia, received an NHMRC-ARC boosting dementia research grant to test 5,000 yeast mutants to search for genes that regulate autophagy.[2]
Over 180 autophagy genes were screened in the yeast model revealing 4 genes that reduce levels of beta amyloid aggregates. Dr Bharadwaj then analysed brain samples and discovered that gene expression of PRKAG2 is increased 3-fold and its protein levels positively correlated with beta amyloid accumulation in the brain.
It has long been thought that autophagy activation is a mitigating response to beta amyloid accumulation in the Alzheimer’s disease brain, but Dr Bharadwaj has discovered a counterintuitive result.
“The scientific question was: ‘How do you find a particular gene or protein that you can activate and clear amyloid?’ We found a gene that activates amyloid removal but is dysregulated in the Alzheimer’s brain,” said Dr Bharadwaj.
“Because autophagy is like a washing machine, clearing up all the garbage, we thought that by activating autophagy, it would clean better. But we found there is a defect somewhere. It’s like the washing machine’s taking in more and more dirty clothes, but it's not washing them. So, amyloid is getting stuck in the whole system.”
“Increased autophagy doesn’t clear out amyloid plaque so we will do more research to show that lowering activity of certain pathways might actually be more beneficial,” said Dr Bharadwaj.
While it’s not the result Dr Bharadwaj had hoped to find, he is committed to pursuing answers, inspired by witnessing a close family member with dementia.
“Ten years ago, I realised that despite an aging population and so many diagnosed neurological diseases, families don’t have options. It’s frustrating that despite decades of research, we still can’t define what causes dementia and there are no efficient drugs to stop or reverse the progression,” he said.
Despite challenges like the COVID-19 pandemic impacting international collaborations, Dr Bharadwaj has continued to strengthen efforts with researchers globally. He is also turning his attention to childhood dementia.
“Engaging with families affected by childhood dementia has been incredibly rewarding. Our findings not only contribute to scientific knowledge but also provide hope and support to those facing these rare disorders.”
“It turns out that a lot of cases of childhood dementia are caused by disorder of the autophagy pathway, the same as in Alzheimer's. So, basically, if there’s anything wrong with your autophagy, you're going to have dementia,” he said.
Next steps
Dr Bharadwaj is continuing his research in Alzheimer’s disease and childhood dementia. He has initiated a national biomarker study bringing together clinicians and paediatric neurologists across Australia. Working with Perth Children’s Hospital and SA pathology, he is developing prognostic blood biomarkers for childhood dementia and is also investigating gene biomarkers in childhood dementia with Adelaide University.
Advancing his work in Alzheimer’s disease, Dr Bharadwaj is investigating small molecules as drug candidates and hopes to engage more with drug developers and potentially startups and private investors. Dr Bharadwaj will also continue mentoring junior academic staff, supervising students and plans to develop his own independent research team.
- Chief investigator: Dr Prashant Bharadwaj
- Administering institution: Edith Cowan University
- Grant information: NHMRC-ARC Dementia Research Development Fellowship (2016–2022), $446,770.90.