The natural presence of antibodies against A has been reported in intravenous immunoglobulin (IVIg); thus, IVIg has been considered as a possible AD treatment. could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being analyzed and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD. strong class=”kwd-title” Keywords: Alzheimer disease, disease-modifying drugs, anti-amyloid, anti-Tau, individualized therapeutic frameworks Genistein Introduction Alzheimer disease (AD) is one of the greatest medical care challenges of our century and is the main cause of dementia. In total, 40?million people are estimated to suffer from dementia throughout the world, and this number is supposed to become twice as much every 20?years, until approximately 2050. 1 Because dementia occurs mostly in people older than 60?years, the growing expansion of lifespan, leading to a rapidly increasing quantity of patients with dementia, 2 mainly AD, has led to an intensive growth in research focused on the treatment of the disease. However, despite all arduous research efforts, at the moment, you will find no effective treatment options for the disease.3,4 The basic pathophysiology and neuropathology of AD that drives the current research suggests that the primary histopathologic lesions of AD are the extracellular amyloid plaques and the intracellular Tau neurofibrillary tangles (NFTs).5 The amyloid or senile plaques (SPs) are constituted chiefly of highly insoluble and proteolysis-resistant peptide fibrils produced by -amyloid (A) cleavage. A peptides with A38, A40, and A42 as the most common variants are produced after the sequential cleavage of the large precursor protein amyloid precursor protein (APP) by the 2 2 enzymes, -secretase (BACE1) and -secretase. Nevertheless, A is not created if APP is usually first acted on and Genistein cleaved by the enzyme -secretase instead of -secretase.6 According to the amyloid hypothesis A production in the brain initiates a cascade of events leading to the Rabbit Polyclonal to OR2AG1/2 clinical syndrome of AD. It is the forming of amyloid Genistein oligomers to which neurotoxicity is mainly attributed and initiates the amyloid cascade. The elements of the cascade include local inflammation, oxidation, excitoxicity (excessive glutamate), and tau hyperphosphorylation.5 Tau protein is a microtubule-associated protein which binds microtubules in cells to facilitate the neuronal transport system. Microtubules also stabilize growing axons necessary for neuronal development and function. Abnormally hyperphosphorylated tau forms insoluble fibrils and folds into intraneuronic tangles. Consequently, it uncouples from microtubules, inhibits transport, and results in microtubule disassembly.6 Although in the amyloid hypothesis, tau hyperphosphorylation was thought to be a downstream event of A deposition, it is equally probable that tau and A act in parallel pathways causing AD Genistein and enhancing each others toxic effects.3 Progressive neuronal destruction prospects to shortage and imbalance between numerous neurotransmitters (eg, acetylcholine, dopamine, serotonin) and to the cognitive deficiencies seen in AD.5 All of the already established treatments that are used today try to counterbalance the neurotransmitter imbalance of the disease. The acetylocholinesterase inhibitors (AChEIs) which are approved for the treatment of AD are donepezil, galantamine, and rivastigmine.4,5 Their development was based in the cholinergic hypothesis which suggests that this progressive loss of limbic and neocortical cholinergic innervation in AD is critically important for memory, learning, attention, and other higher brain functions decline. Furthermore, neurofibrillary degeneration in the basal forebrain is probably the primary cause for the dysfunction and death of cholinergic neurons in this region, giving rise to a common presynaptic cholinergic denervation. The AChEIs increase the availability of acetylcholine at synapses and have been proven clinically useful in delaying the cognitive decline in AD.7 A further therapeutic agent approved for moderate to severe AD is the low-to-moderate affinity, noncompetitive em N /em -methyl-d-aspartate (NMDA) receptor antagonist memantine.4,5 Memantine binds preferentially to open NMDA receptorCoperated calcium channels blocking NMDA-mediated ion flux and ameliorating the dangerous effects of pathologically elevated.