Several competing hypotheses attempt to explain the underlying cause; the two predominant hypotheses are the amyloid beta (Aβ) hypothesis and the cholinergic hypothesis.The oldest hypothesis, on which most drug therapies are based, is the cholinergic hypothesis, which proposes that Alzheimers disease is caused by reduced synthesis of the neurotransmitter acetylcholine. The loss of cholinergic neurons noted in the limbic system and cerebral cortex, is a key feature in the progression of Alzheimers. The 1991 amyloid hypothesis postulated that extracellular 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 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 at least the earliest symptoms of Alzheimers disease by 40 years of age. A specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for Alzheimers disease. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain. Genetic
Only 1–2% of Alzheimers cases are inherited (autosomal dominant). These types are known as early onset familial Alzheimers disease, can have a very early onset, and a faster rate of progression. Early onset familial Alzheimers disease can be attributed to mutations in one of three genes: those encoding amyloid-beta precursor protein (APP) and presenilins PSEN1 and PSEN2.
Delirium and depression can be common among individuals and are important to rule out.Psychological tests for depression are used, since depression can either be concurrent with Alzheimers disease (see Depression of Alzheimer disease), an early sign of cognitive impairment, or even the cause.Due to low accuracy, the C-PIB-PET scan is not recommended as an early diagnostic tool or for predicting the development of Alzheimers disease when people show signs of mild cognitive impairment (MCI). The use of 18F-FDG PET scans, as a single test, to identify people who may develop Alzheimers disease is not supported by evidence. Prevention
There are no disease-modifying treatments available to cure Alzheimers disease and because of this, AD research has focused on interventions to prevent the onset and progression. There is no evidence that supports any particular measure in preventing Alzheimers, and studies of measures to prevent the onset or progression have produced inconsistent results. Epidemiological studies have proposed relationships between an individuals likelihood of developing AD and modifiable factors, such as medications, lifestyle, and diet. There are some challenges in determining whether interventions for Alzheimers disease act as a primary prevention method, preventing the disease itself, or a secondary prevention method, identifying the early stages of the disease. These challenges include duration of intervention, different stages of disease at which intervention begins, and lack of standardization of inclusion criteria regarding biomarkers specific for Alzheimers disease. Further research is needed to determine factors that can help prevent Alzheimers disease.