Ray Das

Summarizing and Modeling the TREM2 signaling pathway as it relates to key features of Alzheimers' Disease

Started Nov. 6, 2021

Abstract or project description

Alzheimer’s Disease (AD) is the most common form of Dementia, contributing to almost 60-70% of cases worldwide [1]. The patients suffering AD face memory loss, inability to learn new things, hallucinations, paranoia and severe cases from communication and speech loss and inability to swallow. The defining features of AD are neurofibrillary tangles of aggregated hyperphosphorylated tau proteins and amyloid plaques composed of amyloid beta peptides. The interplay of ageing, environmental toxins, and genetic factors further complicates the risk of AD. Over the past few years, the impact of rare genetic factors such as variants of triggering receptor expressed on myeloid cells-2 (TREM2) on LOAD (Late Onset Alzheimer’s Disease) neuropathology has been the subject of several studies [3]. Numerous findings in literature suggest the correlation between TREM2 and the accelerated hyperphosphorylation and aggregation of hyperphosphorylated tau proteins. Deficiency of TREM2 leads to accelerated levels of phosphorylation of tau proteins which increases the levels of neuronal stress kinase associated with AD [4]. Additionally, emerging evidence suggests that ApoE-TREM2 interaction might be responsible for regulating various aspects of AD pathology. TREM2 acts as a binding site for ApoE which further plays an important role in pathophysiology of AD [5].  In this review we summarise the relation between TREM2 signalling pathway and main hallmarks of  AD with the goal to gain a better insight into the pathogenesis of AD and the impact of TREM2 on it.