Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer’s Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (Aβ). Data from both AD and TBI studies suggest that microglia play a central role in Aβ accumulation after TBI. This paper focuses on the current research on the role of microglia response to Aβ after TBI. 1. Introduction Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer’s Disease (AD). The interest grew from several lines of evidence, including epidemiological studies that demonstrated an association of TBI and the development of AD later in life [1–7] and autopsy studies that showed acute and chronic AD-like pathology in TBI victims [8, 9]. While most of the studies investigating the association of AD and TBI have focused on the accumulation and clearance amyloid-β (Aβ) [2, 8, 9], chronic neuroinflammation is also a common feature of AD and TBI, and microglia likely play a central role [10, 11]. In AD, microglia are recruited to newly formed Aβ plaques, where microglial activation functions as a double-edged sword, promoting beneficial responses such as Aβ clearance [12–14] while also eliciting a proinflammatory response [12]. Similar patterns of microglia activation have been demonstrated both acutely and chronically after TBI [15, 16]. This paper will explore the current research on the role of microglia response to Aβ after TBI. Although there are few studies that directly examine microglial reaction to trauma-induced Aβ, data from TBI and AD experimental and human studies will be used to make an argument for a central role of microglia in acute and chronic responses to Aβ-mediated secondary injury after TBI. 2. General Microglial Response after TBI TBI is a disease process in which mechanical injury initiates cellular and biochemical changes that perpetuate neuronal injury and death over time, a process known as secondary injury. Secondary injury begins minutes after injury and can continue years after the initial insult. Mechanisms implicated in secondary injury after TBI include glutamate excitotoxicity, blood-brain barrier disruption, secondary hemorrhage, ischemia, mitochondrial dysfunction, apoptotic and necrotic cell death, and inflammation [17]. As the primary mediators of the brain’s innate immune response to infection, injury, and disease, microglia react to injury within minutes. In fact, microglia may represent the first line of defense
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