Neurofibrillary tangles are composed of paired helical filaments (PHF). In normal, non-demented aging, the number of tangles in each affected cell body is relatively low and restricted to the olfactory nucleus, parahippocampal gyrus, amygdala and entorhinal cortex. As the non-demented individual ages, there is a general increase in the density of tangles, but no significant difference in where tangles are found. The other main neurodegenerative contributor commonly found in the brain of patients with AD is amyloid plaques. However, unlike tangles, plaques have not been found to be a consistent feature of normal aging. Role of oxidative stress
Cognitive impairment has been attributed to oxidative stress, inflammatory reactions and changes in the cerebral microvasculature. The exact impact of each of these mechanisms in affecting cognitive aging is unknown. Oxidative stress is the most controllable risk factor and is the best understood. The online Merriam-Webster Medical Dictionary defines oxidative stress as,  "physiological stress on the body that is caused by the cumulative damage done by free radicals inadequately neutralized by antioxidants and that is to be associated with aging." Hence oxidative stress is the damage done to the cells by free radicals that have been released from the oxidation process. Compared to other tissues in the body, the brain is deemed unusually sensitive to oxidative damage. Increased oxidative damage has been associated with neurodegenerative diseases, mild cognitive impairment and individual differences in cognition in healthy elderly people. In normal aging, the brain is undergoing oxidative stress in a multitude of ways.
Familial benign copper deficiency, also known as Familial benign hypocupremia is a rare genetic disorder which is characterized by hypocupremia that causes symptoms such as epilepsy, hypotonia, seborrheic skin, thriving failure and mild anemia. Radiological findings include tibia and femur spurring. Transmission is thought to be either autosomal dominant or X-linked dominant.Symptoms are caused by a familial tendency of having low levels of copper within the body and can be improved (treated and managed) with oral supplements of copper.It has been described in members of a 3-generation Hungarian family. == References ==