**1. Introduction**

Nowadays, Alzheimer's disease (AD) is one of the most common causes of dementia in the United States [1]. Alois Alzheimer discovered AD in 1907 and characterized AD as amyloid plaques, brain atrophy, neurofibrillary tangles, loss of neurons and synapses, and dystrophic neurites in histopathology [2].

Microglia are the resident immune cells in the CNS. They derive from erythromyeloid progenitor cells and then migrate to the brain [3]. Developing and adult microglia demonstrate distinct morphological features as ramified or ameboid [4], which was proved by recent comprehensive transcriptomic analyses [5]. Relative analyses also demonstrate the heterogeneity, abundance, steady state in embryonic, postnatal, juvenile, and adult mouse models [6, 7]. They are also featured as self-renewing, which requires several factors such as colony-stimulating factor-1 receptor (CSF1R) and transforming growth factor β (TGF-β) [8–10]. Moreover, the murine signature of microglia in AD was present in human microglial subtypes, especially clusters 4, 5, 7, and 8. Among which, cluster 7 stands out in the

consequence of its high expression of AD gene decrease in the tissue sections in both AD dementia and pathological AD [11]. This can be a diagnostic standard for AD when the frequency of cluster 7 was diminished.

Hippocampus is an elongated structure that is part of the cerebral cortex [12]. It is one of the most severely affected structures in neurodegenerative diseases like AD [13]. Hippocampus, along with its accessory structure, was suggested to be related to space [14, 15], time [16, 17], and the creation of declarative memories (memories that can evoke conscious awareness and be verbalized) [18].

Hippocampus is vulnerable to the harmfulness of diseases such as epilepsy, hypoxia, ischemia, or encephalitis [18]. The entorhinal cortex is usually the first region that demonstrates tau pathology in AD patients [18]. Somatostatinpositive interneurons are also found lost in the hippocampus of AD patients [19]. In AD patients, degenerative cholinergic neurons in the basal forebrain were proved to lead to dysfunctional cholinergic neurotransmission in regions like hippocampus [20].
