Alzheimer’s Disease (AD) and Oxidative Stress Relationship

Alzheimer’s Disease (AD) and Oxidative Stress Relationship Alzheimer’s disease (AD) is a neurodegenerative disease which causes a lethal twist in the structural integrity, and a roadblock in the function of brain, this eventually channel the situation to degeneration and shrinkage of brain, and override the control of brain over other parts of the body, and comes to the final closing remark of the disease- death. Studies done on the topic have corroborated that the disease is not reversible, and the only patch of hope is slowing down its progress. But as the disease advances through mid stage and evolves into severe AD, the condition of patient becomes pathetic and care giving becomes more painful. Studies have reported that notable symptoms of AD are seen only after 60 years of age, even though the disease has started before that. Initial symptoms are loss of short term memory- being forgetful about the recent events, and gradually over a period of time patient seems more absent –minded about the environment, things which are chemically etched in the long term memory begins to be erased, and the final stage starts pushing the patient into severe AD which is tremendously pathetic. Studies have proved that loss of function of neurons is the cause of AD. A closer look into the aspect revealed a complex set of events that precede the neuronal degeneration- oxidative stress and imbalance in homeostasis, formation of roadblocks in communication, falling apart of integrity and death of neurons. This enabled to go beyond the findings of superficial studies done and hypothesis developed, and helped to delve much deeper into the inner workings and mechanism of the disease. Hypotheses developed to explain mechanism of AD are: amyloid cascade hypothesis, cholinergic hypothesis and tau hypothesis. Amyloid cascade hypothesis says, APP- Amyloid Precursor Protein, a transmembrane protein involved in main roles of growth, survival and repair of nerve cells- is snipped at wrong places by an enzyme called secretase, leadi ng to the formation of amyloid ÃŽ ² peptides which accumulates to form plaques- amyloid plaques- and bind to synapses blocking the communication channel, eventually causes memory loss. According to cholinergic hypothesis, downward drift in the levels of acetylcholine in brain is the cause for Alzheimer’s disease. Loss of function of cholinergic neurons was found in Alzheimer’s disease patients. Shift in the level of acetylcholine happens due to the lack of two enzymes involved in synthesis and breaking down of acetylcholine. This will lead to loss of function of neurons; brain’s functionality falls apart, and eventually leads to symptoms of Alzheimer’s disease. Tau hypothesis approaches the problem in another perspective, tau protein- a protein associated with microtubules in nerve cells- gets hyperphosphorylated, this enables cross linking among tau protein units, and they back off from being attached to the microtubules. This causes loss of structural i ntegrity of nerve cells, and they collapse and clump to form tangles- neurofibrillary tangles. Studies conducted focusing on the inner workings of these hypothesis have found that oxidative stress is the reason that enhances plaque and tangle formation, repair mechanisms in cells are unable to solve the situation as the oligomer formation and cross linking are predominantly made by non peptide bonds. In another study, amyloid ÃŽ ² peptides have shown close relation with some causes of mad cow disease. Studies related to genetics of AD have found the link between APOE gene on chromosome 21 and the disease. APOE gene codes for apolipoprotein, and one among its functions is breaking down of APP. APOE has variants, APOEÃŽ µ4 is the one which codes for less active protein whose capacity to break down APP is sluggish. People with this variant gene are more tend to develop AD in later stages of life, and any abnormality related to chromosome 21 also results in AD over a period of time.