This paper reviews our research studies during the past 17 years on the relationship of cerebral protein dense microspheres (DMS), termed spherons, and senile plaques (SP) in the aged human brain and in AD. Initially, correlative anatomical and pathological data suggested that spherons may evolve into SP. This led to morphometric studies which strongly supported the theory. Biochemical studies were undertaken which showed that spherons could be isolated to homogeneity from brain tissue and contained the markers associated with SP. Experiments in vitro with spherons, and with inoculation of spherons into animals, reproduced SP lesion characteristics. To test the validity of using spherons for drug screening, experimental drugs were tested, a few of which are capable of blocking the formation of spheron-induced experimental SP.