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associated proteins. The amyloid core is surrounded by argyrophilic filamentous, rod-shaped, and granular structures derived from dystrophic neuronal processes and presynaptic terminals. They immunoreact for tau protein (see Fig. 5.5). A variable number of reactive astrocytes and activated microglial cells surround the dystrophic neurites (see Fig. 5.5).

A burnt-out or compact plaque contains only an amyloid core (Fig. 5.6).

Neurofibrillary tangles. These argyrophilic structures within the cytoplasm of the pyramidal neurons have a basket-shaped, flame-shaped, or globose form. Some can be detected as bluish fibrillary structures in HE-stained sections. At the electron microscope level, the tangles appear as paired helical and straight filaments. Their major molecular component is abnormally phosphory-lated tau, a microtubule-associated protein. The diseased neurons eventually die, leaving the tangles as the only remnants (ghost neurons). Neuropil threads of degenerating neuronal processes are dispersed throughout the cortex (Fig. 5.7).

Granulovacuolar degeneration and Hirano bodies are found in the pyramidal neurons of the hippocampus. The granulovacuolar degeneration appears as small basophilic cytoplasmic granules within vacuoles. The Hirano bodies are eosinophilic, rod-shaped structures within or adjacent to the cell body (Fig. 5.8).

Loss of synapses. A progressive loss of synaptic connections between neurons is an essential feature of AD pathology.

Loss of neurons in the neocortical areas and hippocampus ranges from moderate to severe and, in some cases, is total. The cortex, depleted of neurons, shows spongiform changes and replacement astrocytosis (Fig. 5.9).

Amyloid angiopathy. Amyloid is deposited in the walls of the small leptomeningeal and cortical arteries and capillaries. Its composition is similar to that of the amyloid in the neuritic plaques (Fig. 5.10).

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Alzheimer's disease. Classic (mature) neuritic plaque. A. The central amyloid core stains positively with Congo red and gives the characteristic Maltese-cross pattern in polarized light, (B) fluoresces in thioflavin S-stained sections in ultraviolet light, and (C) contains P-amyloid peptide (immunostain). D and E. The central core is surrounded by argyrophilic dystrophic neuronal processes (Gallyas silver stain), which (F) immunoreact for tau protein (immunostain). G. Periplaque glial reaction (HE), consists of (H) astrocytes (GFAP-immunostain), and (I) rod-shaped microglial cells (HE-Congo red).

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