Usually, Alzheimer’s disease starts with the build-up of a protein called amyloid beta, which forms plaques between the neurons. Then, tangles form inside the neurons due to the accumulation of another protein called tau. However, just before these events set off, neurons in certain parts of the brain become overexcited and begin to fire excessively.
A recent study published in the journal Scientific Translational Medicine (19 April) has identified those specific neurons that are vulnerable to such hyperexcitability, and which kickstart Alzheimer’s disease.
The memory aides
The scientists saw that vulnerable neurons were present within the hypothalamus, specifically in structures called mammillary bodies in the brain. The mammillary bodies help in recollecting memory.
“We wanted to understand how distinct neuronal populations comprising the mammillary body contribute to pathology and memory function,” Mitchell Murdock, a graduate student at Prof Li-Huei Tsai’s Lab at the Picower Institute of Learning and Memory, Massachusetts Institute of Technology, USA, and one of the lead authors of the paper tells Happiest Health.
Earlier studies have shown that in Alzheimer’s, hyperexcitability of neurons is found in the cortex and hippocampus, which are the primary drivers of emotions and overall functioning.
Read more: 6 interesting facts about the hippocampus
Finding therapeutic targets within these regions is challenging; altering these neurons could be catastrophic as they govern various body functions. Hence, identifying vulnerable neurons in the memory region of the brain was more lucrative, which this study has achieved.
Mammillary malfunction
In their experiments in mice, the researchers of the current study induced five mutations which caused plaque build-up. They used advanced sequencing techniques and saw that the mammillary body had the most amyloid deposition.
“Damage to the mammillary body has been associated with memory impairments,” says Murdoch. Previous studies have shown that dysfunction in this region causes the inability to form new memories (anterograde amnesia).
The researchers also identified the specific hyperactive neurons before amyloid deposition started. “We found that the lateral mammillary body neurons become hyperactive and contribute to memory impairments,” says Murdoch.
They further found that the hyperexcitability of these neurons increased as the mice grew older. “Work by others has suggested anti-epileptic drugs may be a therapeutic strategy to target Alzheimer’s related cognitive decline,” Murdoch says. So the team tested the mice with anti-epileptic drugs to douse the hyperexcitability of the neurons. They observed that it reduced the overactivity.
The researchers will scale up their study by looking at possible therapeutic targets not just for Alzheimer’s but also for other neurodegenerative conditions. They will also investigate how the mammillary body neurons communicate and connect with each other to find new strategies to treat dementia, Murdoch says.
