Alzheimer's disease

'''Alzheimer's Disease (AD)'''  is a brain disease that slowly destroys brain cells. As of now, there is no cure for Alzheimer's disease. With time, the different symptoms of  the disease become more marked. Many people die because of Alzheimer's disease. The disease affects different parts of the brain but has its worst effects on the areas of the brain that control memory, language, and thinking skills. Alzheimer's Disease is the most common form of senile dementia accounting for up to 70% of cases.

The clinical symptoms of AD usually occur after age 65, but changes in the brain which do not cause symptoms and are caused by Alzheimer's, may begin years or in some cases decades before. Although the symptoms of AD begin in older people it is not a normal part of aging.

At this time there is no cure for Alzheimer's, but there are treatments that can help some patients with the signs and symptoms so they do not affect them as badly. There are also treatments which slow down the disease so the damage to the brain does not happen as quickly. There are also certain personal habits that people can learn which may help to delay the onset of the disease.

While it is not yet known exactly what causes Alzheimer's disease, there are a number of risk factors which may make a person more likely to get it. Some of these risk factors are genetic; changes to four different genes have been found which increase the risk.

The current lifetime risk for a 65-year-old person to get Alzheimer's disease is estimated to be at 10.5%. It is the sixth leading cause of death in the United States causing about 83,500 deaths a year. In 2007, there were over 26.6 million people throughout the world who were affected by AD.

Alzheimer's disease was named after Alois Alzheimer, a German psychiatrist and neuropathologist who first described the disease after studying the case of a middle-aged woman, Auguste Deter, who was a patient at a hospital in Frankfurt, Germany in 1906. The disease was named ''Alzheimer's disease'' in 1910 by Dr. Emil Kraepilin a co-worker of Alzheimer.

## Tangles and plaques
]]
Two of the main features found in the brains of people with of Alzheimer's disease, are *neurobrillary tangles* ('tangles' for short), which are made up of a *protein* called *tau*, and *senile plaques* (which are made mostly from another protein called *beta-amyloid*, they are also sometimes called *beta-amyloid bundles* or 'bundles' for short). The tau proteins that form the tangles previously held together a structure inside the neurons called a *microtubule* which is an important part of the neuron; it forms part of the *cytoskeleton* (cell skeleton) which is what maintains a cell's shape, and microtubules plays a part in cell communication.

Both tangles and plaques may be caused by other diseases, such as Herpes simplex virus Type 1 which is being investigated as a possible cause or contributor in developing Alzheimer's. It is not known for sure if tangles and plaques are part of what causes Alzheimer's, or if they are the results.

**Microtubules**

Microtubules are made of a protein called *tubulin*. The tubulin is *polymerized*, which is when molecules form the same shapes over and over again that are linked together in groups, and these groups are linked together. They can form long chains or other shapes; in this case the polymerized tubulin forms microtubules. The microtubules are rigid tubes like microscopic straws which are hollow inside. Microtubules help keep the shape of the neuron, and are inolved in passing signals through the neuron.

**Tau**

Tau is a protein that is found mostly in the neurons of the central nervous system. They help hold together the *microtubules* within the neurons.  and when changes happen in the way the tau proteins are supposed to work the microtubules break apart. The tau proteins which are no longer holding the microtubules together form strands called *fibrils*, which then clump together inside the neuron to make what are called neurofibrillary tangles . These clumps, also known as 'tau tangles', are all that remain after a neuron has died. 
 
 '''Braak Staging of Alzheimer's disease-related neurofibrillary changes.**This is currently used only for research purposes
 Stage
 Neurofibrillary tangles in:
 Symptoms
	
		**I/II**Transentorhinal stage
		Transentorhinal region and entorhinal region
		No symptoms
	
	
		**III/IV'''Limbic stage
		Hippocampal formation and parts of the limbic system and the amygdala
		Beginning Alzheimer's diseaseCognitive impairments: memory problems, spatial cognition
	
	
		**V/VI**Isocortical stage
		Throughout the cerebral cortex
		Dementia: fully developed Alzheimer's disease
	

**Beta-amyloid **

**Beta-amyloid(Aβ)** (also called 'amyloid beta') plaques start with a protein called amyloid precursor protein (APP). APP is one of the proteins that make up a cell's membrane or outer covering, that protects the cell. In this case a neuron.. As it is made inside the cell, APP sticks out through the membrane of the cell.

In different parts of the of cell including the outermost part of the cell membrane, chemicals called enzymes snip the APP into small pieces.  These enzymes that do the snipping are alpha-secretase, beta-secretase, and gamma-secretase.  Depending on which enzyme is doing the snipping and what parts of the APP are snipped, two different things can happen. One that is helpful and one that causes the formation of beta-amyloid plaques.

The plaques are formed when beta-secretase snips the APP molecule at one end of the beta-amyloid peptide, releasing sAPPβ from the cell. Gamma-secretase then cuts the pieces of APP that is left and, still sticking out of the neuron’s membrane, at the other end of the beta-amyloid peptide. After this snipping the beta-amyloid peptide is released into the space outside the neuron and begins to stick to other beta-amyloid peptides. These pieces stick together to form *oligomers*. Different oligomers of various sizes are now floating around in the spaces between the neurons, which may be responsible for reacting with receptors on neighboring cells and synapses, affecting their ability to function.

Some of these oligomers are cleared from the brain. Those that are not cleared out clump together with more pieces of beta-amyloid. As more pieces clump togther the oligomers get bigger larger, and the next size up are called *protofibrils* and the next size after that are called fibrils. After a while, these fibrils clump together with other protein molecules, neurons and non-nerve cells floating around in the space between the cells and form what are called plaques.

**Cerebral amyloid angiopathy (CAA)**

Deposits of beta-amyloid also form in the walls (in the *tunica media*, the middle layer, and  *tunica adventitia* or *tunica externa*, the outer layer) of small and mid-sized arteries (and sometimes veins) in the cerebral cortex and the *leptomeninges* (the *leptomeninges* are the two inner layers - pia mater and arachnoid - of the *meninges*, a protective 3-layer membrane covering the brain.)

CAA is found in 30% of people over the age of 60 years who do not have any dementia but is found in 90%-96% of people with Alzheimer disease and is severe in one third to two thirds of these cases.

## Stages
The first area of the brain to be affected by Alzheimer's is the "transentorhinal region" which is part of the *medial temporal lobe* located deep within the brain.  Neurons start dying in this area first. It then spreads into the adjacent entorhinal cortex (EC) which acts as a central hub, for a widespread network that handles signals for memory and movement(like a main train station with train tracks going to different areas). 
, Germany, where Auguste Deter was committed at age 51, only eight months after her symptoms began.

She was the first person to be diagnosed, with what is now known as Alzheimer's disease, in her case the early-onset type.]]

In 1901, a 51-year-old woman named Auguste Deter, was committed to the City Asylum for the Insane and Epileptic, (*Städtischen Anstalt für Irre und Epileptische*) in Frankfurt am Main, Germany which had the nickname  "Irrenschloss" (Castle of the Insane). She was married and had a normal life until eight months prior to her commitment, when she started having psychological and neurological problems, such as problems with memory and language, paranoia, becoming disorientated and having hallucinations.

She was studied by a doctor on staff named Alois Alzheimer (1864–1915).  Alzheimer became interested in her case because of her age; while the effects of senile dementia were known at the time, they usually did not start until a person was in their early to mid-sixties. Her case was also notable because of the rapid onset of dementia, only eight months, from the first reported symptoms, until she was committed.

While conducting one of his examinations of Ms. Deter, he asked her to perform a series of simple writing tasks. Unable to do what was asked such as write her name, she said "I have lost myself, so to speak" ("*Ich habe mich sozusagen selbst verloren*").

Alzheimer left the hospital in Franfkurt in 1902 to begin working with Emil Kraepelin at the Psychiatric University Hospital in Heidelberg-Bergheim, and in 1903 both he and Kraepelin began working at Ludwig-Maximilians-Universität in Munich.

When Ms. Deter died of septicemia on 8 April 1906, Alzheimer was informed and her brain was sent to Munich for him to study. Studying samples of her brain under a microscope he noticed neurofibriallry tangles and bundles made up of beta-amyloid plaque, which are two of the main features of the disease.  On 3 November 1906, Alzheimer presented the results of his findings in Auguste's case at the Conference of South-West German Psychiatrists in Tübingen, and he published his findings in the case in 1907.

In 1910, Emil Kraepelin named the disease 'Alzheimer's disease'. Alzheimer's disease usually beigins affecting people between ages 60–65, in Ms. Deter's case - who was 55-years-old when she died - she had a form of what is now known as ''Early-onset Alzhiemer's disease''.

## Famous cases
Anyone can get Alzheimer's disease, rich people or poor famous people and unfamous people. Some of the famous people who have gotten Alzheimer's disease are former United States President Ronald Reagan and Irish writer Iris Murdoch, both of whom were the subjects of scientific articles examining how their cognitive capacities got worse with the disease.

Other cases include the retired footballer Ferenc Puskás, the former Prime Ministers Harold Wilson (United Kingdom) and Adolfo Suárez (Spain), the actress Rita Hayworth, the Nobel Prize-winner Raymond Davis, Jr., the actors Charlton Heston and Gene Wilder, the novelist Terry Pratchett, politician and activist Sargent Shriver, the Blues musician B.B. King, director Jacques Rivette, Indian politician George Fernandes,
and the 2009 Nobel Prize in Physics recipient Charles K. Kao. In 2012, Nobel Prize writer Gabriel García Márquez was diagnosed with the disease. Former Finnish President Mauno Koivisto died of the disease in May 2017. Country singer Glen Campbell died of the disease in August 2017.

## References
## Other websites 
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