LSD1 gene linked to Alzheimer’s and frontotemporal dementia

09 October 2017

Researchers in the US have found that a protein called Lysine specific histone demethylase (LSD1) could protect against neurodegeneration in mice, and suggest that its function could be compromised in Alzheimer’s disease and frontotemporal dementia (FTD). The results of the study are published today in Nature Communications.

LSD1 is a protein known to be critical in the development of human embryos but little was previously known about its role in brain cells.

To study LSD1, researchers generated a mouse with the LSD1 gene deleted. These mice were unable to produce the LSD1 protein, and their brain function was severely impaired. Scientists observed that the mice had lost brain cells in the hippocampal and cortex regions of the brain, leading to reduced spatial ability, memory problems and issues with muscle coordination.

Scientists also looked at changes in gene expression when the LSD1 protein was absent. The found similar changes in gene expression to those seen in people with Alzheimer’s and FTD. By using this approach, the researchers linked the loss of LSD1 protein to many processes already association with Alzheimer’s, including inflammation and important cell signalling mechanisms.

The team of researchers also looked at brain tissue samples from people with Alzheimer’s disease and FTD. Compared to people without dementia, the researchers found that the LSD1 protein accumulated in tau tangles –one of the biological hallmarks of Alzheimer’s disease and FTD.

Dr David Reynolds, Chief Scientific Officer at Alzheimer’s Research UK said:

“This study is interesting, as it’s one of the first to link the LSD1 protein to Alzheimer’s disease or frontotemporal dementia. Genes in the brain are regulated by complex circuits of on and off switches and this study suggests that LSD1 plays a key role in keeping groups of genes in the brain switched off. When the action of LSD1 is compromised, regulation of genes in the brain could goes array and leads to the development of dementia.”

“Further work is required to understand the exact role LSD1 plays in the diseases that cause dementia, and whether it could form the basis of future treatment approaches.”

“Alzheimer’s disease is the most common cause of dementia, affecting 500,000 in the UK alone and frontotemporal dementia is the second most common cause of dementia in people under the age of 65. There are currently no treatments that can stop or slow the progression of either Alzheimer’s or frontotemporal dementia, and this can only be made possible through ongoing investment in dementia research.”