Abstract: The mechanism of AD remains uncovered: The current mainstream doctrine in Alzheimer’s disease (AD) is the amyloid cascade hypothesis. According to this hypothesis, amyloid-β (Aβ) deposition is the main reason for neurofibrillary tangles formation and synaptic dysfunction. However, treatments with antibodies against such targets did not manage to improve cognitive decline and leave some questions regarding the theory of amyloid plaques. Extensive evidence indicates that several pathology changes occur before the appearance of Aβ and tau aggregates. One of the changes is the assault in oligodendrocytes and as a consequence a breakdown of the myelin sheath which is associated with early AD (Dong et al., 2018). Notably, chronic neuroinflammation with sustained activation of microglia and astrocytes may lead to lesion in white matter tracts and disrupt the communication between neurons. Microglia activation and their associated chronic release of inflammatory cytokines in AD subjects attenuate its capacity to clear toxic and harmful substances from the brain which may also underlie the myelin damage. In addition, it was suggested that microglia and immune-related pathways can act as early mediators of synapse loss and dysfunction that occur in AD models before plaques formation. Microglia can exhibit a classically activated phenotype (M1) which exerts toxic effects by secreting proinflammatory cytokines or an alternative activated phenotype (M2) involved in the maintenance of central nervous system homeostasis, phagocytosis of apoptotic bodies or cells, releasing neurotrophic factors, and reducing proinflammatory cytokines. Studies demonstrated that M2 phenotype markers, in contrast to M1 markers, could be modulated in adult microglia, depending on the microenvironment and therefore, have a potential therapeutic effect in neuroinflammation for review see (Tang and Le, 2016.) Apart from resident microglia, another type of microglia has been identified in the brain that originates from monocyte precursor cells from the bone marrow referred as ‘microglia-like” cells. The bone marrow-derived microglia-like cells may cross the blood-brain barrier and migrate into the brain in a chemokine-dependent manner (Kawanishi et al., 2018). In AD, bone marrow-derived cells can access the Aβ-laden brain in higher numbers, as demonstrated in APP23 transgenic mice versus age-matched non-transgenic control mice. Microglia, especially bone marrow derived microglia, has been recently thought to play important roles in internalizing and phagocytizing Aβ oligomers. The invading cells exhibit hematopoietic phenotypes heterogeneously scattered throughout the brain. Hematopoietic stem cells that enter the brain affect brain homeostasis through the secretion of hematopoietic growth factors and cytokines and promote brain repair by increasing neurogenesis