June 19, 2024

I, Science

The science magazine of Imperial College

Researchers have discovered that low levels of the protein NPTX2 and a build-up of amyloid plaques in the brain may play a role in dementia.

A new insight into the memory loss and cognitive decline seen during Alzheimer’s disease has been uncovered by an international team led by John Hopkins University. The team found a direct link between a decline in cognition and the presence of protein clumps in the brain called amyloid plaques, together with low levels of a protein known as NPTX2. The lack of NPTX2, as well as the accumulation of amyloid plaques act to disrupt certain signals in the brain which are thought to be vital for certain cognitive and motor functions.

Large amounts of the amyloid protein are always found in the brains of those suffering from Alzheimer’s, and so it was previously thought to be a cause of memory loss and confusion. However, brain imaging studies and autopsies have now shown that people can have high levels of amyloid without exhibiting any symptoms of the disease, suggesting it is not just the build-up of amyloid plaques that causes altered brain activity.

Instead, the team speculated that the change in neurological function might be linked to a reduction in the levels of ‘immediate early genes’. These act as the pacemakers of the brain, synchronising the activity of cells by inhibiting their activity so that they subsequently fire at the same time. These synchronised pulses are the brain waves familiar on EEG scans, and one type known as gamma oscillations are understood to be important for memory and decision making.

“It’s like bringing the network back into balance” says Dr Mick Craig, of the University of Exeter Medical School, who was part of the team. “If there is a lot of excitation then you’ll turn on this gene which will make the inhibitory cells be more active, to balance out the previous excitation. It’s almost like a homeostatic response.”

By investigating a library of archived human brain tissue samples, the team found significantly reduced levels of the protein encoded by the NPTX2 immediate early gene in those affected by Alzheimer’s. Most importantly, Dr Craig explains that, “The amount of reduction of NPTX2 actually correlates with how much mental functions are impaired.”

What’s more, the team also found that a lack of NPTX2 alone did not necessarily affect cell function, indicating it was in fact the combination of the amyloid plaques and reduction in NPTX2 that appeared to be causing cognitive issues by disrupting gamma oscillations in the brain. “But why that happens we’re not entirely sure yet”, Dr Craig adds.

It is not currently clear whether the presence of amyloid in conjunction with reduced levels of NPXT2 is causing the dementia seen in Alzheimer’s, or if it is simply a symptom of the disease. Much more research is therefore required before it can be considered for treatment in the future.

“If you didn’t know how smoking caused lung cancer and you looked at someone’s house you might conclude that the more ashtrays they have the more likely they are to have lung cancer, but if you remove all the ashtrays you aren’t going to stop them smoking”, explains Dr Craig.

However, this study does provide researchers with a new focus for investigating Alzheimer’s. Such research is of growing urgency, as there is presently no treatment for the disease, and the number of people with dementia is set to rise to over 1 million by 2025. 

Madeleine Finlay is studying for an MSc in Science Communication at Imperial College London.

Banner image: surgeon analysing brain scans, nimon