A special type of senile plaque, possibly an initial stage

Abstract

It is customary to distinguish “primitive”, “classic” and “compact” (“burned out”) senile plaques in Alzheimer's disease and senile dementia of the Alzheimer type (SDAT). Primitive plaques are characterized by altered neurites without accumulation of amyloid, classic plaques by an amyloid core surrounded by altered neurites and compact plaques by amyloid without pathological neurites. Here we describe a further type of plaque in which no amyloid or obviously altered neurites could be found by light microscopy with appropriate stains. This type of plaque was found mainly in the lateral entorhinal region and could be recognized by a slightly more intense staining and an altered texture of the neuropil in a spherical area having the same size as an early or mature plaque (100–150 μm in diameter). In nonserial paraffin sections (3–4 μm thick), a dark, silverpositive cell measuring 10–12 μm in diameter was found in the center of 49 out of 400 such plaques (about 12%), which is the expected frequency if one assumes that every plaque contains such a cell and measures itself about 125 μm. In fact, the reconstruction of 15 plaques (from four different patients) by means of serial sections demonstrated the presence of a central cell in each of them suggesting that this cell is an essential component of this plaque type. The central cell did not react with antibodies against cells of the mononuclear phagocyte lineage, such as alpha-1-antichymotrypsin, alpha-1-antitrypsin, leucocyte common antigen and lysozyme. However, it was consistently stained using the lectinRicinus communis agglutinin-1 (RCA-1), which is known to stain specifically microglia in the normal human brain. We assume that the type of plaque we describe might correspond to a very early step of plaque development and that they are possibly formed even before the primitive plaques mentioned above. We further suggest that such very early lesions might be caused by abnormal activity of microglial cells.