Molecular Properties of Paired Helical Filaments and Senile Plaque Amyloid Fibers in Alzheimer’s Disease

Abstract

In a disorder as complex and enigmatic as Alzheimer’s disease, numerous distinct research strategies must be applied simultaneously. While some experimental approaches will provide information about secondary events in the disease process, it is hoped that other strategies will yield clues to the fundamental biological process that initiates the neuronal degeneration. Most current investigations of the biological aspects of Alzheimer’s disease address one or more of three broad questions. The first question regards the etiologic event(s) that initiate the progressive loss of selected brain neurons. Research strategies in this area include molecular genetic investigations of the chromosomal locus and identity of an abnormal gene in hereditary forms of Alzheimer’s disease; the search for an infectious pathogen; and the study of the role of environmental toxins in this disease. The second broad question concerns the molecular mechanism of cell death, once the initiating event(s) have taken place, whether they are genetic, infectious and/or toxic. The third question is that of the identity of the degenerating neurons as to location, functional class and neurotransmitter status. This latter question in Alzheimer’s disease has received the most experimental attention during the past decade since it appears to offer the earliest chance of developing a therapy that could ameliorate symptoms of the disease. With the rapid development of molecular genetics and neuro-virology in recent years, experiments aimed at the first question are also accelerating.