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Alzheimer’s disease is devastating both for those who suffer from it and for those who love them. It is also expensive. It’s estimated that the current worldwide cost of coping with Alzheimer’s is $818 billion. A cure for Alzheimer’s is not available and current treatments for the disease focus on mitigating symptoms rather than eliminating causes. Recent research has provided evidence that the memory loss associated with Alzheimer’s may be preventable and reversible. Now, new research published in the Proceedings of the National Academy of Sciences reports on a gene therapy treatment that stopped the development of Alzheimer’s disease dead in it’s tracks.

The destruction of neurons that is the root case of Alzheimer’s disease and other types of dementia begins with the formation of plaque deposits in the brain that are built from beta amlyoid peptides. Defective variants of a type of protein called tau protein gather on the beta amyloid deposits. The tau proteins cause inflammation in the brain and destroy surrounding neurons.

Early-stage clinical trials have shown that the antibody aducanumab is effective in destroying the beta amyloid deposits that serve as the gathering place for the defective tau proteins. The new research carried out by a team at Imperial College London describes a gene therapy treatment that prevents the beta amyloid deposits from being formed.

The researchers identified a gene called PGC-1α that interferes with the production of beta amyloid peptides. They directly tested the effect of PGC-1α on the development of Alzheimer’s disease with transgenic mice that are genetically engineered to produce elevated levels of amyloid beta peptides.

The neural destruction associated with Alzheimer’s disease first appears in the hippocampus (an area of the brain involved in memory) and the cortex (an area involved in higher cognitive functions such as thinking and reasoning). The researchers delivered the PGC-1α gene to the hippocampus and cortex of the transgenic mice with a lentivirus which is a type of virus that can inject genetic material into other cells.

The hypothesis that was tested in the study was that the lentivirus would deliver the PGC-1α gene into cells in the hippocampus and cortex where it would interfere with the production of the beta amyloid peptides that play a critical role in the development of Alzheimer’s disease.

The researchers tested this hypothesis with four groups of mice. The strain of mice that are engineered to produce elevated levels of amyloid beta peptides are known as APP23 mice. One group of APP23 mice, the PGC-1α group, had a lentivirus with the PGC-1α gene surgically placed in in their hippocampus and cortex. The control APP23 mice received a lentivirus that did not have the PGC-1α gene. The two lentivirus treatments (with and without the PGC-1α gene) were mirrored in two groups of mice that do not develop Alzheimer’s disease because they do not produce elevated levels of amyloid beta peptides (called wild-type mice). The four groups of mice were tested four months after receiving the lentivirus treatments in order to give the lentivirus time to work.

The effects of the PGC-1α treatment on memory were examined with an object location test and a novel object test. In an object location test a familiar object in the mouse’s environment is moved to a different location. If the mouse remembers where the object had been before it was moved, it will spend more time examining the object after it is moved. In a novel object test a new object is placed in the mouse’s environment. If the mouse remembers its environment, it will recognize that the new object was not there before and will spend more time examining it.

Remember that the APP23 mice produce elevated levels of the beta amyloid peptides that lead to Alzheimer’s disease. If treatment with the PGC-1α gene interferes with the formation of these peptides and thereby retards the development of Alzheimer’s, the PGC-1α group of APP23 mice should perform better on the memory tests than the control APP23 mice that did not receive the PGC-1α treatment.

This is exactly what was found. The control APP23 mice displayed markedly impaired memory in both the object location and novel object tests. In comparison, the PGC-1α APP23 mice showed no memory impairments on either memory test and their performance on the tests was the same as the two groups of wild-type mice who did not develop Alzheimer’s disease.

The memory tests indicate that treatment with the PGC-1α gene prevented the development of Alzheimer’s disease by interfering with the formation of beta amyloid peptides. The researchers delved more deeply into this issue by examining the brain tissue of the mice that were in the study.

There was a 19.1% reduction in beta amyloid peptides in the cortex and a 30% reduction in the hippocampus of the PGC-1α APP23 mice in comparison with the control APP23 mice. Beta amyloid plaque buildup was reduced by 43% in the cortex and 51% in the hippocampus of the PGC-1α APP23 mice in comparison with the controls. The PGC-1α gene was successful in interfering with the production of beta amyloid peptides.

In addition, the inflammation surrounding beta amyloid plaques that contributes to the destruction of neurons in Alzheimer’s disease was markedly reduced in the PGC-1α APP23 mice in comparison with the control APP23 mice.

Looking directly at the destruction of neurons, the researchers compared the APP23 mice that developed Alzheimer’s to the wild-type mice that did not. They found that the APP23 mice with Alzheimer’s disease had 30% fewer neurons in an area of hippocampus. There was no significant loss of neurons in the APP23 mice that were treated with the PGC-1α gene. In other words, mice that are genetically engineered to develop Alzheimer’s disease but are treated with the PGC-1α gene showed the same amount of neural destruction as mice that did not develop Alzheimer’s.

Story Source: The above story is based on materials provided by FORBES