An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease

摘要: Observations, in Alzheimer's disease, the pattern of nerve cell damage and loss, pathology, microchemistry immunology senile plaques neurofibrillary tangles alterations blood vessels are drawn together into a hypothesis that attempts to explain pathogenesis progression disorder. At heart this lies defect brain barrier function and/or structure within cerebral cortex may be cause vessel amyloidosis common many patients with disease. Age-related allow for terminals limited formation cortex; formed cortical subcortical cells which project or near damaged vessels/senile plaques. Uptake "neurotoxin" at affected retrograde transport perikarya causes formed; their accumulation leads perikaryal changes culminating death loss. Loss cortically projecting areas subcortex such as nucleus basalis, locus caeruleus dorsal raphe, terminate on vessels, further dysfunction, new plaque continued loss subcortex. Once started, process could self-perpetuating initial site lie amygdala/hippocampus putative pathogenic agent accessing via olfactory pathways.