16- CYTOSKELETON

The gradual loss of brain function that characterizes Alzheimer's disease seems to be due to two main forms of nerve damage: Nerve fibers grow tangled (neurofibrillary tangles) protein deposits known as plaques build up in the brain

Amyloid plaques and neurofibrillary tangles (NFT)

Alzheimer's Disease is characterized by the formation of beta-amyloid plaques, as shown here. Senile plaques appear as small collections of dark, irregular, thread-like structures often with a brownish material in the center. The central core is represented by amyloid and the irregular, beaded linear structures represent abnormal neurites (small dendrites and axons with degenerative changes). However, tt has been hypothesized that the most dangerous form beta-amyloid may be smaller groups of a few pieces, rather than the large plaques themselves. The small clumps are suggested to synapse signaling and possible

trigger immune system inflamation.

Beta-amyloid is a fragment of a protein that is snipped from amyloid precursor protein (APP), a surface protein produced by healthy cells. Much is still unknown about APP, such as its precise role in normal physiology. Many possibilities have been reported. It has been suggested that APP may be a receptor, and/or that it may serve as a link between kinesin molecular motors and synaptic vesicles. Roles as an adhesion protein, and a function relating to promotion of neurite growth have also been proposed. Gene transcriptional activity has been attributed to APP as well.

Beta-amyloid is cleaved by beta- and gamma- secretase enzymes.

In a healthy brain, these beta-amyloid fragments are broken down and eliminated. However, in AD, these sticky fragments accumulate and fold into hard, insolube clumps/fibrils, forming plaques on the surface of the neuron.