Over the years, there has been tons of research exploring the exact causes of Alzheimer’s disease. Researchers have hypothesized that a combination of lifestyle, environmental, and genetic factors could play a role. Plaques and tangles – proteins in the brain – were also implicated. Research performed over the past decade found a strong genetic link between ApoE4 and Alzheimer’s. But, shares a recent WEHI news release, a research team examining neurodegeneration in fruit fly models recently discovered that a gene called TOMM40 could be a factor. 

Unpacking the Genetic Connection

TOMM40 and ApoE4 are actually genetic neighbors. In the past, the research has focused largely on ApoE4. However, recent studies found that TOMM40 mutations cause TOMM40 protein to be overproduced. This can lead to brain shrinkage – whether or not someone has ApoE4 mutations. 

Intrigued by this finding, WEHI researchers decided to explore excess TOMM40 protein in fruit fly models of neurodegeneration. The team genetically modified the fruit flies to overproduce TOMM40. Careful evaluation showed that the excess protein caused neuron death, with worsening degeneration linked to higher protein levels. Further exploration found that cellular apoptosis – a specific type of cell death – was occuring. 

The authors also found that TOMM40 overproduction caused the TOM complex formation to become overly active. This complex formation normally plays a role to import essential proteins into mitochondria. When overly active, the TOM formation triggers cellular apoptosis.

More research is most certainly needed on TOMM40, its connection to cellular apoptosis and Alzheimer’s disease, and the mechanisms of Alzheimer’s disease as a whole. This does present an avenue for researchers to look into in humans and, potentially, offers a route for therapeutic development in the future. 

Interested in reading more? Take a look at the full study findings published in Scientific Reports. 

A Brief Overview of Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative disorder and is considered the most common form of dementia. Risk factors include being older in age, being female, having a family history of Alzheimer’s disease, poor sleeping and exercise patterns, and past head trauma. This disease affects the parts of the brain which control thought, language, and memory. Symptoms and characteristics include changes in mood, behavior, and personality; difficulty thinking, planning, reasoning, or completing familiar tasks; impulsivity; and memory loss. No cures exist for Alzheimer’s disease. Therapies such as memantine and cholinesterase inhibitors may help preserve memory and cognition.