Alzheimer's disease is a brain disorder that gradually impairs memory and cognitive abilities, eventually leading to the inability to perform even the simplest tasks, making it a significant threat to the mental and physical health of the elderly population. According to epidemiological statistics, the global number of individuals with AD dementia, prodromal AD, and preclinical AD were estimated at 32, 69, and 315 million, respectively. Together, they constitute 416 million individuals across the AD continuum, accounting for 22% of all individuals aged 50 and above. Considering predementia stages, the number of individuals with AD is much larger than previously reported in available literature[1]. Currently, there are no effective medications for Alzheimer's disease, and the cost of dementia care for elderly patients is exorbitant, posing a heavy burden on society, families, and individuals. This realization has prompted our team to recognize the necessity of improving this situation. Upon reviewing literature from PubMed, we found that APOE4 is the strongest genetic risk factor for Alzheimer's disease,roughly 14% of people carry at least one ApoE4 gene. Individuals with two copies of the ApoE4 allele face a tenfold increase in the risk of developing Alzheimer's disease compared to those with the typical ApoE3 allele, with onset occurring as early as 70 years of age and often with more severe symptoms[2]. Moreover, APOE4 is linked to damaging lipid droplets in Alzheimer's disease microglia[3]. A recent study from Yigong Shi's team revealed that LilrB3 is an APOE4-specific immune cell surface receptor. LilrB3 is highly expressed in lymphocytes and plays a role in the clearance of β-amyloid (Aβ) protein. The interferon-stimulated gene (ISG) activation triggered by LilrB3-APOE4 interaction may ultimately hinder microglial phagocytic function, promote Aβ deposition, and thereby increase the risk of Alzheimer's disease (AD) onset[4].

Major Depressive Disorder (MDD) is a severe mental health condition characterized by persistent feelings of sadness, loss of interest in activities, and various emotional and physical problems. Globally, approximately 280 million people suffer from depression, accounting for 3.8% of the total population. In China, about 95 million people are affected by depression, with around 280,000 committing suicide each year, 40% of whom have severe depression. In recent years, the prevalence of depression among adolescents has significantly increased, reaching 15-20%[1,2]. Recent studies have shown that the coupling of serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN) plays a crucial role in the pathophysiology of depression. The interaction between SERT and nNOS leads to a decrease in serotonin levels in the synaptic cleft, triggering depressive symptoms. A study demonstrated that selectively uncoupling SERT from nNOS significantly increases serotonin levels in the synaptic cleft, providing rapid relief from depressive symptoms. This novel approach provides a new target for developing effective antidepressant therapies[3].