Alzheimer’s disease is an age-linked neurodegenerative disorder characterized by marked dementia.
Describe Alzheimer’s disease and its effect on the brain
- Alzheimer’s disease (AD) is the most common form of dementia and was first described by German psychiatrist Alois Alzheimer in 1906.
- There is no cure for AD, which worsens as it progresses and eventually leads to death. Current treatments only help with the symptoms of the disease.
- A small number of cases of AD are inherited and usually have an onset before age 65. This form of the disease is known as early-onset familial AD.
- AD is associated with deposits of amyloid-beta peptide, called plaques, and aggregates of the microtubule-associated protein tau, called tangles, in the brain, which contribute to neuron death.
- amyloid-beta peptide: A peptide of 36–43 amino acids that is processed from the Amyloid precursor protein, best known as a component of amyloid plaques in association with Alzheimer’s disease.
Examples of common symptoms of AD include difficulty remembering recent events and, as the disease advances, confusion, irritability, aggression, mood swings, trouble with language, and long-term memory loss.
Alzheimer’s disease (AD), also known in medical literature as Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him.
Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer’s can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer’s is predicted to affect 1 in 85 people globally by 2050.
Symptoms and Prognosis
Although Alzheimer’s disease develops differently for every individual, there are many common symptoms. Early symptoms are often mistakenly thought to be “age-related” concerns or manifestations of stress. In the early stages, the most common symptom is difficulty in remembering recent events. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behavior and thinking abilities, often followed by a brain scan if available.
As the disease advances, symptoms can include confusion, irritability, aggression, mood swings, trouble with language, and long-term memory loss. As the sufferer declines they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Since the disease is different for each individual, predicting how it will affect the person is difficult. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years. On average, the life expectancy following diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis.
The cause for most Alzheimer’s cases is still essentially unknown (except for 1% to 5% of cases where genetic differences have been identified). Several competing hypotheses exist trying to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalized neuroinflammation.
In 1991, the amyloid hypothesis postulated that amyloid beta (Aβ) deposits are the fundamental cause of the disease. Support for this postulate comes from the location of the gene for the amyloid beta precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down syndrome) who have an extra gene copy almost universally exhibit AD by 40 years of age. Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain. Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology with spatial learning deficits.
Amyloid Plaque Formation: Enzymes act on the APP (Amyloid precursor protein) and cut it into fragments of protein, one of which is called beta-amyloid and its crucial in the formation of senile plaques in AD
In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by ageing-related processes in later life to cause the neuronal withering of Alzheimer’s disease. N-APP, a fragment of APP from the peptide’s N-terminus, is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21). DR6 is highly expressed in the human brain regions most affected by Alzheimer’s, so it is possible that the N-APP/DR6 pathway might be hijacked in the ageing brain to cause damage. In this model, beta-amyloid plays a complementary role, by depressing synaptic function.
Brain Scans: This is a combination of two brain diagrams in one for comparison. In the left normal brain, in the right brain of a person with Alzheimer’s disease.