Causes Of Alzheimer's Disease (1)

Causes of Alzheimer's Disease Scientists believe that for most people, Alzheimer's disease is caused by a combination of genetic, lifestyle and environmental factors that affect the brain over time. Less than 5 percent of the time, Alzheimer's disease is caused by specific genetic changes that virtually guarantee a person will develop the disease. Although the causes of Alzheimer's aren't yet fully understood, its effect on the brain is clear. Alzheimer's disease damages and kills brain cells. A brain affected by Alzheimer's disease has many fewer cells and many fewer connections among surviving cells than does a healthy brain. As more and more brain cells die, Alzheimer's leads to significant brain shrinkage. When doctors examine Alzheimer's brain tissue under the microscope, they see two types of abnormalities that are considered hallmarks of the disease: Neurofibrillary Tangles. Neurofibrillary tangles are insoluble twisted fibers found inside the brain's cells. These tangles consist primarily of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. In Alzheimer's disease, however, the tau protein is abnormal and the microtubule structures collapse leading to failure of the transport system. This failure is also strongly implicated in the decline and death of brain cells. Some groups of neurons are preferentially affected by tangles in AD. For example, neurofibrillary tangles frequently occur in areas of the hippocampus (small organ located within the brain's medial temporal lobe) that are involved in processing experiences prior to storage as permanent memories. This correlates with the clinical deficits observed in the early stages of AD in learning and in the creation of new memories, as well as with the relative preservation of established memories. Plaques. Plaques are more complex; they consist of extracellular deposits of amyloid material in the grey matter of the brain and are associated with swollen, distorted neuronal processes called dystrophic neurites. Degenerative neural structures and an abundance of microglia and astrocytes can be associated with plaque deposits. These clumps of proteins called beta-amyloid may damage and destroy brain cells in several ways, including interfering with cell-to-cell communication. Plaques start as innocuous deposits of nonaggregated, non-neurotoxic β-amyloid (diffuse plaques). However, in some individuals they undergo an orderly sequential transformation into the mature neuritic plaques that are associated with the development of AD. Although the ultimate cause of brain-cell death in Alzheimer's isn't known, the collection of betaamyloid on the outside of brain cells is a prime suspect.

Risk factors Age Increasing age is the greatest known risk factor for Alzheimer's. Alzheimer's is not a part of normal aging, but your risk increases greatly after you reach age 65. The rate of dementia doubles every decade after age 60. People with rare genetic changes linked to early-onset Alzheimer's begin experiencing symptoms as early as their 30s. Family history and genetics Your risk of developing Alzheimer's appears to be somewhat higher if a first-degree relative — your parent or sibling — has the disease. Scientists have identified rare changes (mutations) in three genes that virtually guarantee a person who inherits them will develop Alzheimer's. But these mutations account for less than 5 percent of Alzheimer's disease. Most genetic mechanisms of Alzheimer's among families remain largely unexplained. The strongest risk gene researchers have found so far is apolipoprotein e4 (APoE4), though not everyone with this gene goes on to develop Alzheimer's disease. Other risk genes have been identified but not conclusively confirmed. Down syndrome Many people with Down syndrome develop Alzheimer's disease. Signs and symptoms of Alzheimer's tend to appear 10 to 20 years earlier in people with Down syndrome than they do for the general population. A gene contained in the extra chromosome that causes Down syndrome significantly increases the risk of Alzheimer's disease. Sex Women seem to be more likely than are men to develop Alzheimer's disease, in part because they live longer. Lifelong learning and social engagement Studies have found an association between lifelong involvement in mentally and socially stimulating activities and a reduced risk of Alzheimer's disease. Low education levels — less than a high school education — appear to be a risk factor for Alzheimer's disease.

Lifestyle and heart health There's no lifestyle factor that's been definitively shown to reduce your risk of Alzheimer's disease. However, some evidence suggests that the same factors that put you at risk of heart disease also may increase the chance that you'll develop Alzheimer's. Examples include: -Lack of exercise -Obesity -Smoking or exposure to secondhand smoke -High blood pressure -High blood cholesterol -Poorly controlled type 2 diabetes -A diet lacking in fruits and vegetables Past head trauma Undergoing severe or repeated traumatic brain injuries (TBI) Environmental factors Exposure to some environmental contaminants, such as toxic metals, pesticide, and industrial chemicals

References Mackenzie IR. Senile plaques do not progressively accumulate with normal aging. Acta Neuropathol (Berl)1994;87:520-5. Gomez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol 1997;41:17-24. MacGill, Markus. "What's to know about Alzheimer's disease?." Medical News Today. MediLexicon, Intl., 13 Feb. 2018. Goldman L, et al., eds. Alzheimer disease and other dementias. In: Goldman-Cecil Medicine. 25th ed. Philadelphia, Pa.: Saunders Elsevier; 2016