Alzheimer’s Mouse Model Aids Research into Sex-specific Memory-making Brain Cell Decline

Nanyang Technological University (NTU Singapore) and National University of Singapore (NUS) scientists have conducted a joint study to investigate why, in mice, female brains are more predisposed to Alzheimer’s disease and other neurodegenerative diseases. 

The study sought to provide insights into why women developed Alzheimer’s-related symptoms earlier and exhibited a faster decline in memory compared to men. By experimenting on mice brain samples, the research team found that as female mice age, they experienced a faster decay in their information processing ability compared to male mice, resulting in weaker memory formation and increased memory loss. 

The study was led by Assistant Professor Ch’ng Toh Hean from NTU’s Lee Kong Chian School of Medicine and Associate Professor Sajikumar Sreedharan from the NUS Yong Loo Lin School of Medicine’s Department of Physiology, and included NTU research fellows Dr Sheeja Navakkode and Dr Jessica Gaunt.

The findings showed that the brains of female mice with the Alzheimer’s genetic mutation were less flexible, or ‘plastic’, in adapting to new information and forming new memories. 

This lowered plasticity of the brain’s synapses - the connections between brain cells, or neurons - likely contributes to greater cognitive impairment and increased vulnerability to Alzheimer’s disease in females, say the scientists.

“It is well-documented that Alzheimer’s disproportionately affects more women than men, with women at a higher risk of developing the disease. For a long time, scientists have thought that this discrepancy was because women on average live longer than men, but our study based on mice models provided evidence that the processing time of information in female brain synapses declines much earlier compared to male brain synapses,” said Asstistant Professor Ch’ng.  

“More recent studies suggest that there are biological reasons beyond longevity that explains the sex discrepancy, such as genetics, hormones, and lifestyle impact. However, although the associated risk factors are clear, the exact reasons why female brains show this faster decline - and are hence more susceptible to Alzheimer’s - require further study,” he said. 

The findings were published in Aging Cell in November 2021. The joint study was funded by a Singapore Ministry of Education Academic Research Fund Tier 3 and the NTU Nanyang Assistant Professorship and supported by the NUS Joint Research Programme (NUSMED-FOS).

Paper titled ‘Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease’, published in Aging Cell, 18 November 2021. DOI: 10.1111/acel.13502

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