Date of Award

1999

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

Abstract

Alzheimer's disease (AD) is clinically characterized by progressive mental decline. The pathomorphology of AD includes the accumulation of abnormal filaments, known as neurofibrillary tangles or NFT, within the nerve cells and of extracellular deposits of amyloid fibers surrounded by dystrophic neurites that form senile plaques. Many inflammatory proteins have been found in association with lesions in AD brain, but the role of the inflammatory reactions in AD pathogenesis is not known. The goal of this study was to analyze the relationship between the inflammatory and neuropathological changes in AD brain through examining the density of lesions immunoreactive for inflammatory proteins C-reactive protein (CRP), amyloid P component (AP), and complements (C1q, C4c, C3d, C5) in the hippocampus, the entorhinal cortex, and the temporal cortex at different stages of severity of pathological changes (NFT formation) according to the Braak method. NFT were visualized by an immunocytochemical technique with specific antibodies recognizing microtubule-associated protein tau and inflammatory proteins. Neurons were stained using the Nissl procedure. NFT and neuronal density were determined by the Williams and Rakic three-dimensional counting method. Inflammatory proteins were found in AD brain from the earliest stages of neurofibrillary changes. The density of NFT immunoreactive for inflammatory proteins increased with the severity of neurofibrillary changes and was inversely related to the neuronal density. The study suggests that the progressive nature of the disease is related to a concomitant progressive development of the inflammatory reactions in AD brain and that the inflammation is an integral part of the pathogenesis and may contribute to the development of the disease starting from the initial stages of AD.

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