An Overview of Multipronged Strategies of Alzheimer’s Disease in Humans and Developments in Drug Therapies

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia in older adults, characterized by memory decline, cognitive impairment, and behavioral disturbances. Pathologically, AD is defined by extracellular accumulation of amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Although aging remains the predominant risk factor, the disease arises from a multifactorial interaction of genetic predisposition, oxidative stress, environmental influences, and lifestyle factors. Dysregulation of the Wnt signaling pathway, which regulates synaptic function and neuronal plasticity, has been increasingly associated with AD pathogenesis. This pathway’s impairment contributes to synaptic loss, neuroinflammation, and cognitive decline. Conventional therapies for AD primarily alleviate symptoms without halting neurodegeneration, prompting growing interest in natural and bioactive compounds as alternative therapeutic agents. Plant- and marine-derived metabolites exhibit potent antioxidant, anti-inflammatory, and acetylcholines-terase-inhibitory activities that may counteract multiple pathogenic mechanisms in AD. Several studies have demonstrated that these natural compounds can suppress Aβ aggregation, downregulate BACE1 expression, and protect neurons against oxidative and inflammatory damage. Moreover, peptide- and protein-based molecules, particularly those from natural sources, are gaining attention due to their biocompatibility and ability to target specific molecular pathways involved in neurodegeneration. However, challenges such as difficult purification processes, variable bioavailability, and inconsistent clinical outcomes limit their translation into approved therapies. Despite these obstacles, natural compounds provide a promising, multitargeted, and relatively safer approach compared with synthetic drugs. Overall, AD development reflects a complex interplay of genetic, environmental, and lifestyle factors. Exploring natural products and peptide-based therapeutics may therefore offer new strategies to delay disease progression and enhance neuronal resilience, highlighting their potential as complementary options in the future management of Alzheimer’s disease.