Innate immune cells have garnered increased interest in recent neurological studies due to their role in the etiology and pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). It is well known that the buildup of amyloid-beta (Aβ) plaque and neurofibrillary tangles are classical hallmarks of the AD brain. However, it has been shown that even if plaques and tangles are present, the chances of developing Alzheimer’s disease is not a guarantee.

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Many researchers believe that it is the neuroinflammation that occurs in response to the formation of plaques that is the primary killer of neurons, which leads to cognitive decline (1). Microglia, the resident macrophages of the brain, have been proven to be key regulators of brain development and disruption in their machinery has been linked to neuroinflammation (2). Given that the primary target of AZTherapies’s ALZT-OP1 drug is microglia, it is necessary to elucidate the properties of these cells and why they are crucial players in neurodegenerative research. Microglia are the main neuroimmune cells of our central nervous system (CNS) and typically have three main functions:

• They are constantly monitoring the environment of the CNS, scanning for any changes
• They are neural housekeepers that help keep a healthy environment in the CNS
• They are neuroprotective and defend the CNS when negative changes are detected

Microglia tend to shift to two different states. In their homeostatic state, sentinel microglia survey the CNS for any changes. Upon activation, microglia can either take up a proinflammatory state that releases molecules that cause neuroinflammation or a neuroprotective state that clears foreign pathogens and returns their environment to homeostasis. In neurodegenerative diseases such as Alzheimer’s disease, microglia have been observed to shift to their proinflammatory state fueling the neuroinflammation in the

CNS. Dr. Tanzi firmly believes that the key to finding a cure to Alzheimer’s disease is to find a way to turn off the neuroinflammatory responses of microglia.

The primary goal of AZTherapies’ pipeline candidates, including ALZT-OP1 for Alzheimer’s disease, is to shift microglia to its neuroprotective state to promote neuronal health. Targeting inflammation in the brain is believed to be the most crucial way to halt progression of neurodegeneration thus alleviating disease pathogenesis (3).

References:
(1)’Crosstalk’ between genes promotes brain inflammation in Alzheimer’s. (2019, July 11). Retrieved from https://www.sciencedaily.com/releases/2019/07/1907 11122705.htm
(2)Lenz, K. M., & Nelson, L. H. (2018, March 21). Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function. Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2018.00698/full
(3)Harnessing the Power of Neuro-Immunology – Our Science. (n.d.). Retrieved from https://aztherapies.com/our- science/