Pathology of AD

Pathology of AD

The most severe pathology is usually seen in the hippocampus, temporal cortex, and nucleus basalis.
The most important microscopic findings are neuritic "senile" plaques and cytoplasmic neurofibrillary tangles (NFTs). These two lesions accumulate in small numbers during normal aging of the brain but occur in quantitative excess in the dementia of AD.

Neuritic plaques contain
• A central core that includes Ab amyloid, proteoglycans, Apo E, a1 antichymotrypsin, and other proteins.
• The plaque core is surrounded by the debris of degenerating neurons, microglia, and macrophages

Ab amyloid
• 4.2-kDa protein of 39 to 42 amino acids
• Proteolytically from a larger transmembrane protein (amyloid precursor protein, APP) through cleavage by two enzymes termed b and g secretase
• Normal function of Ab amyloid is unknown.
• APP has been shown to have neurotrophic and neuroprotective activities.

The accumulation of Ab amyloid in cerebral arterioles is termed amyloid angiopathy.

NFTs
• silver-staining,
• twisted neurofilaments in neuronal cytoplasm that represent abnormally phosphorylated tau (t) protein and
• Appear as paired helical filaments by electron microscopy.

Tau is a microtubule-associated protein that may function to assemble and stabilize the microtubules that convey cell organelles, glycoproteins, and other important materials through the neuron. The ability of tau protein to bind to microtubule segments is determined partly by the number of phosphate groups attached to it. Increased phosphorylation of tau protein may disturb this normal process.