Alzeheimer Disease

Amyloid, or senile, plaques are dense, insoluble deposits of amyloid-beta proteins, which are fragments of amyloid precursor proteins (APP), a transmembrane neuronal protein. As these proteins are enzymatically broken down, they clump together, forming the dense structures identifiable as amyloid plaques. These plaques primarily accumulate in the association cortices and hippocampus.

Neurofibrillary tangles develop when microtubule tau proteins become hyperphosphorylated and aggregate within the neuronal cells. These tangles break down the neurons' ability to transport molecules along the axon. Neurofibrillary tangles initially form in the medial aspect and pole of the temporal lobe, especially the hippocampus. With increasing disease progression, they spread throughout the cortex, beginning in the high-order association regions and less commonly in the primary motor and sensory regions.

Neuroimaging provides an excellent means of grossly examining the brain. It allows for volumetric measurements of individual structures and can be repeated over time as a coarse means of measuring disease progression. Neuroimaging also allows for exclusion of many reversible causes of dementia. Magnetic resonance imaging (MRI) is the preferred modality of imaging because it allows for excellent 3-dimensional visualization, especially of the hippocampus. The most common findings are cortical atrophy, dilated ventricles, and accentuated cortical sulci. On the T1-weighted MRI shown, extensive hippocampal atrophy has occurred on the right side (see arrow).

Computed tomography (CT) is not as useful as MRI in diagnosing or following the progression of Alzheimer's disease, although it is commonly used as a first-line modality in patients who present with dementia. The principal findings are similar in both modalities and changes over time are useful; however, on a CT scan, the etiology of cerebral atrophy is more difficult to discriminate between Alzheimer's disease and normal aging. The CT scan shown here demonstrates several areas of calcification within the basal ganglia, the result of extreme degeneration in a patient with Down's syndrome and early Alzheimer's disease

Current treatment regimens for Alzheimer's disease focus on symptomatic therapy, as no proven disease-modifying therapies exist. The standard medications are cholinesterase inhibitors (ChEIs) and partial N-methyl-D-aspartate (NMDA) antagonists. ChEIs act by preventing the breakdown of acetylcholine, because cholinergic systems that modulate information processing are thought to be impaired. Partial NMDA antagonists are thought to improve the signal-to-noise ratio of glutamatergic transmission. Both classes of medication may be used together and provide modest symptomatic improvement but do nothing to prevent disease progression. Frequently, psychotropic medications are also included to treat the secondary symptoms (eg, depression, agitation, sleep disorders) that develop. Image included with permission and copyrighted by First DataBank, Inc.