Enormous progress has been made towards understanding the pathophysiology of Alzheimer’s disease (AD) over the recent years through the advancement of research in the field of AD research. However, the unavailability of an appropriate drug for treatment raises several questions and scores the lake of thorough understanding the regulatory mechanisms underlying the disease pathophysiology and thereby the needs of further research for deeper understanding and uncover the hidden complexity. Most of the drugs that have been designed and proceed to clinical trials are focused on clearing of the aggregates of amyloid beta and the neurofibrillary tangles that are made of phosphorylated, while the focus on neuroinflammatory pathways is also emerging. Other pathological pathways that have profound regulatory roles underlying AD dementia include APOE mediated cholesterol transportation and metabolism, TREM2 mutation, DNA methylation, histone modification and non-coding RNAs etc. This review is particularly focus on how APOE, TREM2, DNA methylation, histone modification and non-coding RNAs contribute to neuroinflammation and leads to dementia of AD.