Patients often misplace various items repeatedly, show a decline in job performance, forget directions to previously familiar locations, struggle to come up with appropriate words while speaking, and become increasingly passive and aloof. Ultimately, these patients lose the capacity for functioning autonomously and, therefore, they are forced into complete dependency. They deteriorate into a vegetative state, become bedridden, and die often from infections or pulmonary embolus. While the complete pathogenesis of the illness remains unknown, however, some elements of its pathology are clear. The etiological search for any illness begins with its cellular pathology, and what is found on examination of Alzheimer's brains is a loss of neurons in regions of the cerebral cortex and the hippocampus, ultimately leading to diffuse atrophy in those areas.
Neurofibrillary tangles are bundles of filaments that collect inside the neurons.
These are paired helical filaments composed of a hyperphosphorylated form of a protein called tau. These neuritic plaques have, therefore, been the primary target of therapeutics, and so a further word on their nature is warranted. As stated earlier, microglia and astrocytes form a part of the neuritic plaques. These are cells that travel to sites of brain injury for purposes of restoration and repair. Its aggregation in the brain, whether diffusely or within amyloid cores of neuritic plaques, is a cardinal feature of AD, and its amount in the brain correlates with the patient's cognitive impairment.