Alzheimer’s disease (also known as just Alzheimer’s or AD) is a progressive, degenerative and ultimately fatal brain disease, in which cell to cell connections in the brain are lost. It is the most common form of dementia, and is generally (though not exclusively) diagnosed in patients over the age of about 65.
The disease was first identified by Alois Alzheimer as early as 1906, although up until the 1960s it was usually referred to as “senile dementia” and considered a normal part of ageing. Scientific interest in Alzheimer’s was only re-awakened in the 1960s and 1970s as the consequences of an ageing society began to be examined, and it was during the 1980s that research first focused on the toxic proteins amyloid in plaques and tau in tangles.
The most commonly recognized symptom of AD is an inability to acquire new memories and difficulty in recalling recently observed facts, but it is by no means the only symptom. As the disease advances, symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and ultimately a gradual loss of bodily functions and death. A number of non-invasive life-style habits, such as mental stimulation, physical exercise and a balanced diet, have been suggested for the prevention or delayed onset of Alzheimer’s disease, but no effective treatments to delay or halt the progression of the disease are as yet available.
Alzheimer’s does not affect all memory capacities equally: short-term memory (the ability of hold information in mind in an active, readily-available state for a short period of time) is the first to go; next comes episodic memory(memory of autobiographical events); then semantic memory (memory of the meanings of words and facts about the world); and finally procedural memory(how to perform tasks and skills). As the disease advances, parts of memory which were previously intact also become impaired, and eventually all reasoning, attention, and language abilities are disrupted.
AD patients tend to display a loss of knowledge of the specific characteristics of semantic categories. Initially, they lose the ability to distinguish fine categories, such as species of animals or types of objects, but, over time, this lack of discrimination extends to broader, more general categories. Thus, at first, an AD patient may see a spaniel and say, “that is a dog”; later, they may just say, “that is an animal”.
Neurologically, AD (and dementia in general) is characterized by a loss of neurons and synapses in the cerebral cortex and certain subcortical regions of the brain. This loss results in gross atrophy of the affected regions, including degeneration in the hippocampus, temporal lobe and parietal lobe, as well as parts of the frontal cortex and cingulate gyrus.
Although there is as yet no consensus on the causes of AD, a couple of promising leads have been discovered. One proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine, which is used in the communication between neurons in the brain. The other main theory, which appears to be gradually becoming the front runner, involves two different proteins, tau and amyloid beta, both of which are active in the normal healthy brain but which run out of control in Alzheimer’s patients. Normal tau protein supplies nutrients to the brain’s nerve cells and stabilizes the microtubules that carry messages through healthy neurons. When damaged, though, the tau protein becomes “tangled” inside nerve cell bodies, shutting off the supply of nutrients to the cell. These neurofibrillary tangles ultimately collapse the neuron’s transport system, thus effectively killing the brain cell. Amyloid beta (or beta amyloid) is another protein used in the normal activity of the brain. But, in the early stages of Alzheimers, it has been observed to form aggregations or deposits, known as amyloid plaques, which serve to disrupt neuronal communication. While high levels of amyloid beta can help predict the risk of Alzheimers, it is the amount of tau protein that correlates more closely with the development and severity of the disease.
The two proteins interact in some (as yet poorly understood) way, but it appears to be the tau protein tangles that are largely responsible for the spread of the disease throughout the brain. As more and more plaques and tangles form in particular brain areas, healthy neuron begin to work less efficiently. Then, they lose their ability to function and communicate with each other, and eventually they die off completely. This damaging process gradually spreads throughout the brain, including the hippocampus, which is essential in forming long-term memories. As the die-off of neurons increases, affected brain regions begin to atrophy and shrink until, by the final stages of Alzheimer’s, damage is widespread and brain tissue has shrunk significantly.
In the 1990s, genetic links to Alzheimer’s began to be discovered, and by the late 1990s the first drug treatments (such as Aricept, Exelon and Reminyl) were approved. In 2004, an NMDA receptor blocker called Ebixa was the first drug to actually slow the decline of patients with moderate to advanced Alzheimer’s. As research continues, more and more genes linked to Alzheimer’s have been identified, including TREM2 and ApoE.
Recent research has investigated the possible benefial effects of insulin on Alzheimer’s patients, with some researchers going so far as to suggest that Alzheimer’s is akin to diabetes of the brain. There is also some evidence that a widely-used cancer drug called bexarotene may help in clearing amyloid plaques, at least in mice. However, there have also been setbacks in treatments, and in 2010 a clinical trial for the beta amyloid blocking drug Semagacestat was halted after it was found to make patients worse, casting some doubt on the theory that amyloid plaques are the principal cause of the disease.