Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with significant memory decline and cognitive impairment. AD is characterized by two classical neuropathological hallmarks, namely the amyloid-beta (Aβ) plaques and neurofibril tangles. Currently, there are no disease-modifying treatments available for AD, except for a couple of the US Food and Drug Administration (FDA)-approved drugs to improve cognitive function by blocking N-methyl-D-aspartate receptors or cholinesterase activity (Panza et al., 2019). While these drugs offer some symptomatic relief against AD, they do little to halt the progression of the disease. For over two decades, the amyloid cascade hypothesis of AD has been the central focus for the development of biomarkers and disease-modifying therapeutic strategies, supported by strong genetic, biochemical and histopathological evidence. Unfortunately, over 15 years of clinical failure with several classes of anti-Aβ drugs that affect the formation, aggregation and clearance of Aβ have made the research community rethink the strategies to develop appropriate treatments for AD (Panza et al., 2019). AD is characterized by a vast heterogeneity in its pathophysiology that is influenced by several risk factors such as aging, lifestyle, and genetic and environmental changes. The complex etiology of the disease, coupled with the failure of past clinical interventions directed at a “fit-for-all” therapy, demands a change in therapeutic strategies for an effective and more favourable outcome against AD. There is thus, a need for the development of tailored/targeted therapy for specific AD subpopulations that share distinct genetic, molecular or pathological properties. In this regard, our perspective discusses three potential molecular biomarkers, namely monoacylglycerol lipase (Mgll), apolipoprotein E4 (APOE4) and the phosphatidylinositol 3-kinase (PIK3)/protein kinase (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway, as prime candidates for targeted therapy.