The Impact of the APOE<i>ε</i>4 on the Number of Neurons and Gene Expression of Degenerating Neurons in the Dorsolateral Prefrontal Cortex in Alzheimer’s Patients

Alzheimer’s disease (AD) is highly prevalent in the elderly population and leads to AD patients’ higher mortality, low life quality, and lead to a huge economic burden on the health system. Even though the APOEε4 gene has been identified as a risk factor for the late onset of AD, there are no studies to examine the impact of APOEε4 on the neural and gene expression mechanisms of cognitive impairment in AD. Our study examined the impact of APOEε4 on AD patients’ cognitive function and the level of a hallmark of AD pathology. This study also examined the impact of APOEε4 on the number of neurons in the dorsolateral prefrontal cortex (DLPFC)and the gene expression of degenerating neurons. This study used data from one publicly available dataset called the Seattle Alzheimer’s Disease Brain Cell Atlas consortium (SEA-AD), including 75 AD patients (M = 88.56 years, SD = 7.89). T-tests revealed a significant difference in participants’ age at death, cognitive status, age of onset cognitive symptoms, cognitive abilities screening instrument score, mini-mental state examination score, montreal cognitive assessment score, and the percentage of Sst chodl, L6 b, and L5/6 NP cells between APOEε4 carriers and non-carriers. Single-cell RNA sequence revealed that APOEε4 led to a significantly less gene expression of the GLRA1 gene in Sst chodl neurons and KCNA1 gene in L5/6 NP neurons. The present findings provide insight for enhancing understanding of the cause of AD and AD’s cognitive impairment from an APOEε4 perspective.