Alzheimer’s disease (AD) is the most common cause of dementia. Until now, none of the approved AD treatments turned out to be a success. AD is unknown but involves genetic, biochemical, and environmental factors. Thus, one of the reasons why single-target-directed drugs have failed to reach clinical trials is the pathological complexity found in AD. It could be better contrasted by the development of Multiple Targeting Directed Ligands (MTDLs), which can modulate simultaneously multiple targets involved in the onset of the pathology. As a new strategy in drug discovery for AD, compared to combination therapies, multifunctional molecules avoid drug–drug interactions, off-target adverse effects, poor patient compliance, and high development costs. Strikingly, overexpression of both targets serves as drivers of the cognitive impairment, leading to synaptic plasticity reduction, autophagy dysfunction, increasing tau pathology, OS, and neuroinflammation, collectively contributing to and/or resulting in age-related cognitive decline and neurodegenerative disease, particularly AD. Here, we synthesized the compound ABS9, a new chemical scaffold with high potency to inhibit both targets. Besides, treatment with ABS9 in SAMP8 mice rescued cognitive decline measured via NORT. Then, we evaluated the Tau phosphorylation in different serines, observing that ABS9 was able to reduce its levels in SAMP8. In addition, the density of dendritic spines and the length of dendritic branches were evaluated, showing an increase in the treated group. Accordingly, markers of synaptic plasticity were also evaluated. Therefore, ABS9 is a potential drug candidate for the AD treatment.