In Alzheimers disease, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neurons transport system. Pathogenic tau can also cause neuronal death through transposable element dysregulation. Disease mechanism
Exactly how disturbances of production and aggregation of the beta-amyloid peptide give rise to the pathology of Alzheimers disease is not known. The amyloid hypothesis traditionally points to the accumulation of beta-amyloid peptides as the central event triggering neuron degeneration. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cells calcium ion homeostasis, induces programmed cell death (apoptosis). It is also known that Aβ selectively builds up in the mitochondria in the cells of Alzheimers-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons.Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimers disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in Alzheimers disease or a marker of an immunological response. There is increasing evidence of a strong interaction between the neurons and the immunological mechanisms in the brain. Obesity and systemic inflammation may interfere with immunological processes which promote disease progression.Alterations in the distribution of different neurotrophic factors and in the expression of their receptors such as the brain-derived neurotrophic factor (BDNF) have been described in Alzheimers disease.
The disease is known to target the hippocampus which is associated with memory, and this is responsible for the first symptoms of memory impairment. As the disease progresses so does the degree of memory impairment. First symptoms
The first symptoms are often mistakenly attributed to aging or stress. Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria for diagnosis of Alzheimers disease. These early symptoms can affect the most complex activities of daily living. The most noticeable deficit is short term memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information.Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract thinking, or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of the early stages of Alzheimers disease. Apathy and depression can be seen at this stage, with apathy remaining as the most persistent symptom throughout the course of the disease. Mild cognitive impairment (MCI) is often found to be a transitional stage between normal aging and dementia. MCI can present with a variety of symptoms, and when memory loss is the predominant symptom, it is termed amnestic MCI and is frequently seen as a prodromal stage of Alzheimers disease. Amnestic MCI has a greater than 90% likelihood of being associated with Alzheimers. Early stage
In people with Alzheimers disease, the increasing impairment of learning and memory eventually leads to a definitive diagnosis.