Alzheimer disease (AD) is the most common cause of dementia in the elderly population. AD is a neurodegenerative disease which usually manifests with onset of impaired intellectual function and altered mood and behavior. Later this disease progresses to memory loss, aphasia and over another 5 to 10 years the patients becomes mute and immobile.
In the familial forms of AD is supported the model in which a peptide called beta amyloid accumulates in the brain over time. Beta amyloid is created when the amyloid precursor protein (APP), which is a transmembrane protein, is cleaved by the enzymes: beta amyloid converting enzyme (BACE) and Y-secretase.
Mutations in APP or in components of Y-secretase lead to familial AD.
Macrophages infiltrate the brain during AD and help clear away these proteins by the process of phagocytosis. Microglia as well help clear away these so called toxic proteins.
Macrophages and microglia express a receptor called TREM2 and even that mutations in TREM2 have been associated with AD, the function of this receptor is unclear.
To discover the role of TREM2 receptor in developing AD scientists from Cleveland Clinic deleted the receptor in mice that develop AD-like disease. Removal of this receptor decreased the formation of the plaques, reduced the inflammation and there were fewer infiltrating macrophages. Macrophages which had no TREM2 receptor demonstrated that were better in phagocyting beta amyloid structures.
Although more studies are needed to create a better idea on the function of TREM2 receptor, these studies suggest that inhibiting the receptor may help stop further damage or neurodegeneration in AD patients.