Oxidative Stress and Neurodegeneration The daily activities for human survival often constitute serious challenges and threats to human health [1] . Stressful life events that are accompanied with psychological and behavioral reactions are believed to predispose people to mental illness [2, 3] . Intense oxygen release could predispose human to stress induced neurodegenerative diseases. Oxygen is a critical element for all living cells or neuron [4] . This essential element is involved in

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... ve phosphorylation to generate adenosine triphosphate (ATP), a vital metabolic process to neuronal maintenance and survival [5, 6] . However, excessive release of oxygen and subsequent oxidative stress have been attributed to the failure of the complex regulatory systems and disruption of cellular homeostatic processes. Oxidative stress could be associated to the imbalance in the equilibrium between oxidant and antioxidant molecules [7] . Predominant activities of prooxidant molecules could lead to a chain of effects that promote further generation of reactive oxygen species (ROS) and free radicals. These molecules are potentially neurotoxic. The high levels of oxidative stress can cause necrosis, ATP depletion and prevent the occurrence of controlled apoptotic death [8] . For normal functioning, the brain requires a high supply of oxygen and glucose to enable continuous generation of ATP pool. Hence, the brain is more susceptible to oxygen overload and free radical generation [9] . 1-2% of O 2 consumed is converted to ROS in a normal condition but in an aged brain or in an oxidative stress induced pathological condition, this percentage could increase dramatically due to a reduction in the level of antioxidants and low regenerative capacity of aged brain [9] . Meanwhile, oxidative stress and free radical generation play pivotal role in redox reactions that result into AD [7]. An age-related memory impairments correlate with a reduction in brain and plasma antioxidants [10, 11] . ROS such as hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), superoxide anions and the highly reactive hydroxyl and monoxide radicals (OH·, NO·) are among the free radicals that constitute high risk to neuronal loss or damage [12] [13] [14][15]. Excessive oxidative activities in AD are characterized by high levels of oxidised proteins, formation of toxic species like peroxides, alcohols, aldehydes, free carbonyles, ketones, cholestenone advanced glycation end products, lipid peroxidation end products and oxidative modifications in nuclear and mitochondrial DNA [16][17][18][19][20][21][22][23][24][25][26]. Epidemiological evidences have shown that inflammation, stroke, hypertension, diabetes, smoking, head trauma, depression, infection, tumors, vitamin deficiencies, chemical exposure, endocrine, immune and metabolic dysfunctions constitute risk factors of neurodegenerative diseases [27,28]. In this minireview, we attempt to summarize the prevalenceof AD, current understanding of pathophysiology, treatment and preclinical research strategies of AD. We review some of the biomarker that has been targeted by drugs to mitigate degeneration of neurons. It is beyond the scope of this paper to provide full review of the broad range of hypothesis or the enormous outpouring of scientific data on AD. Brief Facts about Alzheimer's Disease and its Prevalence Alzheimer's disease (AD) is a chronic progressive disease Abstract Alzheimer's disease (AD) is one of the neurodegenerative diseases that affect millions of people worldwide. AD could rob patients of their ability to recall, reason and carry out executive functions. Pathophysiological studies of AD have revealed the gradual loss of neurons, function and ultimate death of neurons (apoptosis). Mutations, oxidative stress, excitotoxicity, infectious diseases are among the principal causes of neuronal degeneration. Despite the prescription of a wide range of drugs to treat AD, the emergence of effective treatments to halt the progress or reverse this disease has remained elusive for years. Series of preclinical studies have been developed to ensure better understanding of the neurobiology of AD and engender the discovery of new drugs. This review provides an overview on the pathophysiology, pharmacotherapy and preclinical models of AD in an attempt to bring together current research efforts, challenges, achievements and prospect for the discovery of drugs to treat AD. Pathophysiological evidences of this neurodegenerative disease has shown the involvement of multiple neural mechanisms. So far, the research approaches and treatment of this disease still remain largely unsatisfactory. However, there are possibilities of surmounting current challenges with new technology, diagnostic criteria and translational approach that effectively reflect clinical etiology of AD in experimental animals.