Senile Plaque

The plaque is a complex structure found in the neuropil and consists of amyloid, abnormal neurites and glial cells (4). The ^-amyloid which is present in all plaques, is a protein of 1-43 amino acids (5,6). It is clipped out of a larger amyloid precursor protein through a set of complex processes that are under intensive investigation at the present time (7). can exist in various physical conformations, which include soluble, aggregated (but nonfibril-lar), and aggregated fibrillar forms (8,9). In addition to A£, abnormal (dystrophic) neurites are associated with a subset of SP (Fig. 1E-G) and represent degenerated processes of neurons (mainly dendrites) and consist of bundles of fibrillar elements (4,10). The plaques with neurites often have microglia and astrocytes associated with them (4).

Plaques occur in various types. The first classification of plaques was proposed by Terry and Wisniewski (4) who described three types of SP based on electron-microscopic observations. The primitive SP has some amyloid as well as dystrophic neurites, the latter being invisible in the light microscope. The classical SP has a compact core of amyloid surrounded by a zone of abnormal neurites. Finally, the burned out or compact SP is a large mass of amyloid and no neurites are associated with it. These three types of SP can be visualized in sections processed with Bielschowsky silver stain (or a modification thereof) or thioflavine S stain. The amyloid associated with these SP is also congophilic (can be visualized using the Congo red stain under polarized light).

More recently, SPs have been divided into types based on the presence or absence of various features at the light microscopic level. The first of these classifications became possible with the advent of specific antibodies to Immunohistochemistry using these antibodies results in staining of a very large number of plaques, more than any other procedure used (11-13). These im-munostained SPs are of two types (11,14). The diffuse SPs are round or amorphous deposits of aggregated (nonfibrillar) with a granular reaction product and without clear borders (Fig.lA). The compact SPs, on the other hand, are clearly defined, round deposits of fibrillar (Fig. 1B,C), which also stain positively for thioflavine S and Congo red. The presence of a heavy central deposit of amyloid in compact SP, often visualized using thioflavine S or silver stain, defines a cored (Fig. 1C-E) as distinguished from uncored SP. Finally, the presence of dystrophic (abnormal) neurites distinguishes neuritic SP (Fig. 1E-G) from SP without neurites (10,13,15). It is currently believed that the various plaque types represent maturational stages of a single pathological process (16). According to this hypothesis, amyloid is first deposited in the form of diffuse

Fig. 1. Examples of the pathological lesions observed in the brains of patients suffering from Alzheimer's disease. (A) Diffuse Aß-positive plaques visualized using im-munohistochemical techniques. (B) Aß-positive compact plaques. (C) Aß-positive compact plaque with a dense amyloid core (cored plaque). (D) A cored plaque visualized using the thioflavine S stain. (E) Thioflavine S stained cored plaques with a few associated dystrophic neurites (arrow). (F) Thioflavine S stained neuritic plaque. (G) Dystrophic neurites associated with a plaque visualized immunohistochemically using an antibody against a hyperphosphorylated epitope of tau (PHF-1). Neuropil threads (arrows) are also PHF-1 positive. (H) A PHF-1-positive neurofibrillary tangle and neuropit threads (arrows). (I) Thioflavine S stained tangles and neuropil threads (arrow).

Fig. 1. Examples of the pathological lesions observed in the brains of patients suffering from Alzheimer's disease. (A) Diffuse Aß-positive plaques visualized using im-munohistochemical techniques. (B) Aß-positive compact plaques. (C) Aß-positive compact plaque with a dense amyloid core (cored plaque). (D) A cored plaque visualized using the thioflavine S stain. (E) Thioflavine S stained cored plaques with a few associated dystrophic neurites (arrow). (F) Thioflavine S stained neuritic plaque. (G) Dystrophic neurites associated with a plaque visualized immunohistochemically using an antibody against a hyperphosphorylated epitope of tau (PHF-1). Neuropil threads (arrows) are also PHF-1 positive. (H) A PHF-1-positive neurofibrillary tangle and neuropit threads (arrows). (I) Thioflavine S stained tangles and neuropil threads (arrow).

SP. Gradually, this amyloid is transformed to fibrils, which are thought to be toxic to neurons and disruptive to neuronal processes present in the neuropil (8). Still later, dystrophic neurites become associated with the SP, presumably representing degeneration of neuronal components damaged by amyloid.

Although SPs are observed throughout the brain in AD, the heaviest deposits are found within the cerebral cortex. The densest accumulation of SPs are observed in association cortical regions, followed by paralimbic and core limbic regions, respectively (13,17,18). A dense accumulation of SP, particularly the neuritic variety (10), is thought to be a specific marker of Alzheimer's disease since it does not occur in other neurodegenerative disorders (19,20).

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