No abstract

The presence of components of immunoglobulins (Ishii et al. 1975) and complements (Eikelenboom and Stam 1982) in senile plaques suggests that the immunologic mechanisms are involved in the causation of pathologic processes in the brain of patients with Alzheimer's disease. Senile plaques consists of amyloid degenerated neuritis and glia, and exact localization of complements among these tissue elements will provide an important clue to the pathogenesis of the Alzheimer brain. This report deals with light- and electron-microscopic localization of complements in amyloid fibrils of senile plaques by immunoperoxidase histochemistry. The presence of C1q, C4, and C3 is confirmed light-microscopically. At the ultrastructural level, anti-complement C1q, C4, and C3 peroxidase reaction products are exclusively localized on the amyloid fibrils, but no other tissue elements, such as normal or degenerated neurites, neurofibrillary tangles, or glia. The results indicate the presence of immune complex in amyloid fibrils of senile plaques, and little association of complements in senile plaques with neurofilament protein.

A sensitive methenamine silver/Nissl stain was used to study the morphology and relationship of pre-plaques (presumed early senile plaques) in Down's syndrome brains to glial nuclei, capillaries and neuronal perikarya. The larger pre-plaques (greater than 50 microns) usually encompassed all of these tissue elements. However, the smaller pre-plaques (less than or equal to 50 microns) were almost always found immediately adjacent to, or around the cell bodies of neurons (often with associated satellite cells), and they failed to show any consistent, close spatial relationship to the other tissue components. Thus we consider an early stage of pre-plaque formation to be the deposition of amyloid adjacent to the cell body of a morphologically normal neuron. Based on the study of transitional forms, we suggest that the amyloid progressively accumulates around the cell body until the enclosed neuron degenerates. How these pre-plaque lesions might eventually develop into the typical plaque structure is uncertain. Our observations support the theory of a neuronal origin for plaque amyloid.

Using a fluorescent antibody technique, sections of the brains of patients with senile dementia or Alzheimer's disease containing senile plaques were treated with rabbit antihuman immunoglobulins labelled with FITC (fluorescein isothiocyanate, BBL). The senile plaques and the cerebral amyloid angiopathy (drusige Entartung, Scholz, 1938) in the brains of patients with senile dementia or Alzheimer's disease showed specific fluorescence. Control sections from the brains of a girl who died from carcinoma of the stomach and of a female schizophrenic who died from lung abscess, showed only slight fluorescence in a few vessel walls. The presence of components or fragments of immunoglobulins in a senile plaques may mean that immunological factors are involved in their pathogenesis and probably also in that of senile dementia and Alzheimer's disease.

No abstract