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City duo spot Alzheimer’s brain change

Malay Bhattacharya and Sanghamitra Bandopadhyay

New Delhi, Feb. 12: Two computer scientists in Calcutta have spotted previously unknown changes in the brains of patients with Alzheimer’s disease that they say could hold clues about its cause still shrouded in mystery.

Sanghamitra Bandopadhyay at the Indian Statistical Institute and her student Malay Bhattacharyya have used computational techniques to identify changes in a type of genetic material that seem linked to early stages of Alzheimer’s disease.

Both scientists quit formal biology lessons after senior school and neither has ever handled brain cells in a laboratory. But using biological data generated three years ago by US scientists, the ISI team has explored via computer science the activity of short sequences of genetic material called micro-ribonucleic acid, or miRNAs, that play a role in blocking the production of proteins inside cells.

Alzheimer’s disease, a degenerative brain disorder whose precise cause remains unknown, has been traditionally regarded as a condition associated with the brain’s gray matter, mainly composed of neurons or brain cells.

The ISI study, published in the journal Molecular Biosystems , suggests certain changes in the brain’s white matter — involved in passing messages across the nervous system — also appear to be associated with Alzheimer’s disease.

“We see a strong signal exclusively in white matter,” said Bandopadhyay, who had received the Shanti Swarup Bhatnagar Prize, India’s highest science award, in 2010 for her computational studies of miRNAs in cancers. “But we have no idea about its biological significance — that’s something that neurologists will need to investigate,” Bandopadhyay told The Telegraph.

The findings seem to corroborate a role for white matter in Alzheimer’s disease postulated a decade ago by American scientists who had seen alterations in the white matter of brain tissues from patients with the disorder.

Bandopadhyay and Bhattacharyya analysed miRNA data generated three years ago by scientists at the University of Kentucky and identified an miRNA that works in pairs with 15 other miRNAs only in the white matter of patients with Alzheimer’s disease.

“This single miRNA seems to be the hub of a network of miRNAs that are overactive in pairs with the hub only in the white matter — we don’t see this paired activity in the dark matter,” Bhattacharyya said.

Neurologists not associated with the ISI study said these results seem significant but would need to be authenticated through direct biological studies or imaging studies of the brain’s white matter.

“This appears consistent with recent (advanced) imaging studies of brains that have indicated certain levels of loss of integrity, or degeneration, in the white matter,” said Sarada Subramanian, professor of neurochemistry at the National Institute of Mental Health and Neurosciences, Bangalore.

Pravat Mandal, a brain imaging specialist at the National Brain Research Centre in Manesar, Haryana, said one way to authenticate the findings from Calcutta would be to conduct imaging studies specifically on tissues where the miRNA changes were observed.

For an understanding of the significance of the observed miRNA network, Bandopadhyay said, biologists would need to pinpoint the specific proteins that the paired miRNAs block in the white matter.

A cue from computer science to medicine.