Unravelling Alzheimer’s

Recent studies throw much light on changes in the brain that lead to Alzheimer’s disease.

CLICK & SEE

It may have been ascribed a name more than a century ago, but Alzheimer’s disease — the most common form of dementia that makes people forget names, places and things and lose track of time and events irretrievably — still remains a mystery.

Science has so far failed to fully understand the exact cause of this brain disorder, let alone develop a cure. Alzheimer’s strikes at old age, occasional memory lapse being the first symptom. The condition deteriorates rapidly and those suffering from its severest forms may not be able to recognise even their closest family members. Moreover, the patients often experience delusions and hallucinations.

The name “Alzheimer’s disease” entered the medical lexicon in 1907 following a description of the condition by the German physician Dr Alois Alzheimer at a scientific meeting the year before. Dr Alzheimer happened to treat a female patient in 1901 who had some peculiar symptoms: problems with memory, unfounded suspicions about her husband’s fidelity and difficulty in speaking and understanding what was said to her. After her death — which was about five years later — he performed an autopsy on her, of course with her family’s permission. He found that her brain had shrunken dramatically, particularly in the cortex region, the outer layer involved in memory, thinking, judgement and speech.

Scientists may still not know the cause of the disease, but recent advances in neuro-imaging techniques have shown that those suffering from it have two abnormal structures in their brain: plaques formed of deposits of a sticky protein fragment called beta-amyloid, and tangled or twisted fibres of another protein called tau inside the dying nerve cells.

Actually, most people develop plaques and tangles as they age, but those with Alzheimer’s tend to form them on a much larger scale. Ever since the discovery of these unusual elements in the brain of Alzheimer’s patients, scientists have been trying to ascertain their role in triggering as well as in the progression of the disease.

There have been three independent studies recently — two of them involving Indian researchers — that have greatly enhanced scientists’ understanding of Alzheimer’s.

The first, by a team of researchers that included Ganesh Shankar and Tapan Mehta of Harvard Medical School, shows that all the beta-amyloid in an Alzheimer’s patient’s brain is not directly responsible for the disease. The work, led by Dennis Selkoe of the Centre for Neurologic Diseases at Harvard, is the first such study to unlock the cascade of molecular events that lead to this debilitating condition. The team also has researchers from University College, Dublin, and the Royal College of Surgeons in Ireland.

Selkoe and his team observed for the first time that beta-amyloid exists in various forms. While some of these survive as single molecules called monomers, there are others which are formed by two or more molecules of beta-amyloid that stick together and which are soluble. Then there are clumps which are not soluble at all.

Your ads will be inserted here by

Easy Plugin for AdSense.

Please go to the plugin admin page to
Paste your ad code OR
Suppress this ad slot.

The study, recently published in Nature Medicine, came up with an interesting finding. The scientists first isolated beta-amyloid from the brains of Alzheimer’s patients, separating them as monomers, oligomers and insoluble plaque. They then injected these separately into the brains of mice. To their surprise they found that memory was impaired only when soluble beta-amyloid oligomers were administered to the hippocampus (brain region where memory is stored) of the animals.

The exposure to soluble beta-amyloid reduced the density of dendrite spines (that actually receive and transit messages sent by other brain cells) in the hippocampus by almost half. This led the scientists to conclude that soluble beta-amyloid molecules act directly on synapses, the connections between neurons that are necessary for communication in the brain.

When they exposed the mice nerve cells to amyloid plaques from which soluble beta-amyloid had been removed, the researchers found that there was no disturbance in the brain signalling.

“We think that plaques are protective, but it’s the soluble oligomers that interrupt synaptic function,” says Selkoe.

“The study has put yet one more piece into place in the puzzle that is Alzheimer’s,” observes Richard Hodes, director of the US National Institute on Aging that financed the study.

The second study, by Lawrence Rajendran, a post-doctoral student at the Max Planck Institute of Molecular Cell Biology and Genetics at Dresden in Germany, and colleagues looks into the very formation of beta-amyloid. Their work shows that beta-secretase, an enzyme that chops down a molecule called amyloid precursor protein to make beta-amyloid, works only in a tiny compartment inside the brain cell.

Beta-secretase, which is found in the cells of many organs, is an innocent bystander most of the time, Rajendran told KnowHow. “Only when it is inside the endosome — a tiny compartment in brain cells — does it assume a villainous form,” he says. He thinks that if scientists can devise a strategy to attack beta-secretase inside the endosomes, they can control the production of beta-amyloid.

Yet another study by researchers in the UK and Canada, which appeared last week in Nature Cell Biology, says that the best way to treat Alzheimer’s is to trick the brain into not producing the tau protein, which forms the aggregates called tangles. The scientists, who studied the chemistry and structure of the tau protein, designed an enzyme inhibitor which uses a sugar molecule to lower the production of the protein.

With the new insights, scientists hope that the management of Alzheimer’s disease — which is estimated to cost more than $300 billion a year — may become easier. Perhaps there may soon be drugs that can treat the worst of neuro degenerative disorders.

Sources: The Telegraph (Kolkata, India)

2 thoughts on “Unravelling Alzheimer’s”

  1. I found the article informative and interesting. I am wondering which part of the brain that connect to the consciousness! And whether 'the soul' also embedded or somehow linked with the brain?

Leave a Reply

Your email address will not be published. Required fields are marked *