Memories ‘Lost’ In Alzheimer’s May Not Be Lost After All

New research is providing hope that lost memories may simply be blocked, not destroyed

A team at MIT has demonstrated that mice in early stage Alzheimer’s can form memories, but are simply unable to access them. Using a revolutionary technique called optogenetics, they proved that these memories could be retrieved – opening up hope for future treatment of patients with dementia. 

“The important point is, this a proof of concept. That is, even if a memory seems to be gone, it is still there. It’s a matter of how to retrieve it”

Cut off, not lost

Memory loss occurs in early stage Alzheimer’s disease, before characteristic plaques are visible. While long term memory remains accessible for most people with the disease, short term memory quickly becomes a serious problem. In a mouse model of the condition, the research team gave mice a small shock on the floor of a particular chamber. Normal mice showed fear when they were re-introduced to the room, but the Alzheimer’s model mice didn’t appear to remember their experiences. 

However, when the scientists tagged particular engram memory cells with a protein called channelrhodopsin which is light activated, they found they could re-activate these fearful memories in Alzheimer’s mice. This suggests the memories were actually forming, they simply weren’t connected. 

A memory engram cell Credit: RIKEN

“Directly activating the cells that we believe are holding the memory gets them to retrieve it. This suggests that it is indeed an access problem to the information, not that they’re unable to learn or store this memory”

What was going on?

It seems that while memories do form in these mice, the engram cells create fewer dendritic spines connecting these to other cells and enabling memory recall. The input for recall from theentorhinal cortex therefore doesn’t reach the memory cell, and the memory can’t get recalled. 

Optogenetics involves targeting a cell with a precise wavelength of light, which will activate channelrhodopsin proteins and cellular activity 

“If we want to recall a memory, the memory-holding cells have to be reactivated by the correct cue. If the spine density does not go up during learning process, then later, if you give a natural recall cue, it may not be able to reach the nucleus of the engram cells”

Stimulating a connection

After learning that this was happening, the researchers stimulated new connections to form between the entorhinal cortex and the hippocampus by once again using optogenetics and activating entorhinal cells. After a period of activation following memory creation, the memories seemed to stick. However, large scale activation of cells was ineffective suggesting a highly targeted treatment is required. Optogenetics is not currently feasible in humans due to its highly invasive nature, but the data still provides hope that these lost memories could one day be reconnected. 

Read more at NeuroscienceNews