Alzheimer’s gene found by scientists decrease symptoms

Scientists have identified the gene that increases the risk of Alzheimer’s disease up to 12 times and how they can suppress it, a study claims.

ApoE4 is a genetic variant known to increase a person’s chances for developing the neurodegenerative disease. 

The mutant gene is directly linked to brain damage caused by knots of protein within neurons called tau tangles. The tangles were found to less harmful without ApoE4.

They believe targeting the gene could theoretically prevent the neurological destruction caused by Alzheimer’s, for which there is currently no cure. 

An estimated five-and-a-half million people in the United States suffer from Alzheimer’s, according to the Alzheimer’s Association. 

Experts say this discovery could pave the way for treatments that will slow down or halt the disease that causes loss of memory and cognitive function. 

Researchers from Washington University School of Medicine in St. Louis, Missouri, studied ApoE4 after it was first discovered in 1993. 

The gene has been known as a ‘time bomb’ for the disease but has remained a mystery on how it impairs the brain until now. 

The presence of the gene increases the brain damage caused by toxic tangles of a different Alzheimer’s-associated protein: tau. In its absence, tau tangles did very little harm to brain cells.

‘Once tau accumulates, the brain degenerates,’ said senior author Dr David Holtzman, head of the Department of Neurology at Washington University.

‘What we found was that when ApoE is there, it amplifies the toxic function of tau, which means that if we can reduce ApoE levels we may be able to stop the disease process.’ 

Alzheimer’s, which affects one in 10 people over age 65, is the most common example of a family of diseases called tauopathies.  

To find out what effect ApoE variants have on tauopathies, Holtzman and his team turned to genetically modified mice that carry a mutant form of human tau prone to forming toxic tangles.

They compared mice that lacked any version of the gene or were engineered to have one of three human variants, ApoE2, ApoE3 or ApoE4.

By the time they were nine months old, mice carrying the human variants had suffered widespread brain damage.  

The hippocampus and entorhinal cortex, which are responsible for memory, were shrunken, and the fluid-filled space of the brain had enlarged where the dead cells had been.

ApoE4 mice exhibited the most severe neurodegeneration, and ApoE2 the least. The mice that lacked the gene entirely showed virtually no brain damage.

‘ApoE4 seems to be causing more damage than the other variants because it is instigating a much higher inflammatory response, and it is likely the inflammation that is causing injury,’ Holtzman said. 

‘But all forms of ApoE – even ApoE2 – are harmful to some extent when tau is aggregating and accumulating. The best thing seems to be in this setting to have no ApoE at all in the brain.’ 

A follow-up study of brain tissue samples from 79 people who had died from tau-related conditions other than Alzheimer’s showed greater levels of damage in those who had ApoE4. 

The gene transports cholesterol around the body via the bloodstream.

A few, rare individuals lack a functional ApoE gene. Such people have very high cholesterol levels and, if untreated, die young of cardiovascular disease. The lack of the gene in their brains, however, creates no obvious problems.

‘There are people walking around who have no ApoE and they’re fine cognitively,’ Holtzman said. ‘It doesn’t appear to be required for normal brain function.’

These findings suggest that decreasing ApoE specifically in the brain could slow or block neurodegeneration, even in people who already have accumulated tau tangles.

‘Assuming that our findings are replicated by others, I think that reducing ApoE in the brain in people who are in the earliest stages of disease could prevent further neurodegeneration,’ Holtzman said.