Israeli Researchers Link Unique Protein to Age-related Memory Loss

Israeli researchers have zeroed in on a protein linked to long-term memory, allowing them to explore ways to combat memory loss in age-related Alzheimer's and dementia.

Age-related dementia is one of those sad ironies of life: as technology and healthcare advance, so life span has increased – and so have accompanying malaises. Now Israeli researchers from Haifa University have linked age-related Alzheimer's to certain aspects of protein regulation going haywire.

There are two main types of Alzheimer's, similar in symptoms but not in origin. Both involve irreversible advances of mental incapacity.

The rarer form is hereditary. Passing down generations, it is responsible for about 5 percent of cases. This form often appears relatively early, usually among people aged 50 to 60. It can however occur in people younger than that.

The second and more prevalent form of the disease is called Sporadic Alzheimer's Disease. This is primarily related to aging. Now Yifat Segev (supervised by Prof. Kobi Rosenblum) and Prof. Dani Michaelson from Tel Aviv University have shown a correlation between protein production in the body and the advance of Alzheimer's.

Simply put, the more protein production in neurons increases, the better long-term memory is.

Women have it worse

Between 28 percent to 45 percent of people over 90 years old have some form of dementia, depending on gender: women are more likely to develop the malady. Some 45 percent of women over 90 develop the disease compared with 28 percent in men. As age increases, the proportion climbs much faster among women.

No cure has been found to treat any of these forms of the disease. In Israel, about 100,000 are thought to suffer from Alzheimer's, which is about 20 percent of the aged population. It might be worth noting that Alzheimer's can only be definitively diagnosed after death.

One manifestation of Alzheimer's is the lost ability to form new memories. Put another way, when something happens, the sufferer soon forgets. The memory doesn't get "written" into the long-term memory banks.

Prof. Rosenblum's team and other scientists around the world have found that a protein involved in controlling protein production in the body, named eIF2alpha, is directly responsible for the transformation of short to long term memory.

How eIF2alpha affects protein production

Think of eIF2alpha as a valve that increases or decreases general protein production in the body.

Proteins are a huge molecule, yet they are often activated and deactivated by the addition of a very small molecule – a phosphate group. This is called phosphorylation.

Think of phosphorylation as an on/off switch.

In the case of elF2alpha, heavy phosphorylation – the addition of phosphate groups – results in less protein production, and impaired long-term memory.

Why does the production of more protein in neurons improve long term memory?

Basically, because it consolidates the structure of a given memory in our brain. It does not form the memory but instead makes it stronger and immune to disruptions over time.  

The scientists' conclusion: perhaps depressing phosphorylation of  eIF2alpha, using drugs, can improve long-term memory.

As you grow older

As people age, the Israeli scientists have shown, the level of phosphorylated eIF2alpha in the brain increases. Thus long-term memory is impaired.

Now, armed with Israeli government and EU grants, Rosenblum is working on developing drugs or genetic engineering that would constrain the phosphorylation of elF2alpha.

“It won't cure Alzheimer's, but may help postpone its breakout or its expression,” he says.

One huge problem: how to make the cure selective, since elF2alfa affects all protein production in the entire body, Rosenblum explains. One doesn't want to depress protein production in general just to cure memory loss.