Vascular-Related and Mediated Alterations in Alzheimer’s Disease

Abstract

Alois Alzheimer and his contemporaries recognized a vascular component of the disease that now bears his name: Alzheimer’s disease (AD) (1987 translation). In the initial publication, Alzheimer reported the case of a 51 year old with progressive dementia and characteristic neuropathology. The neuropathology detailed after autopsy included: neuron loss, gliosis, neuronal fibrils (paired helical filaments), tangled bundles of fibrils where a neuron had once been (neurofibrillary tangles), and miliary foci of drusen (senile plaques). He also noted vascular changes, including cerebral arteriosclerosis and focal lesions of vessel endothelium. The same year (1987) Fischer suggested that it was not surprising to find neuropathological similarities between demented individuals with arteriosclerotic brain atrophy and those with what is today known as AD (1987 translation). Three years later, Emil Kraepelin (1987 translation) analyzed his own populations grouped according to the presence of presenile dementia, senile dementia, or arteriosclerotic disease, but he was unable to separate the possible roles of arteriosclerotic and senile changes. Among his presenile subjects, most of whom died of heart disease, neuropathologic changes were similar to those reported by Alzheimer, except for the absence of fiber formation. Some subjects exhibited fat in the vessel walls; others did not. Among his senile subjects—most of whom also died of heart attack—arteriosclerotic alterations, enlarged heart, and high blood pressure were common. Included within this senile population were the individuals most severely affected, and who were similar to the subject studied by Alzheimer. Kraepelin (1987 translation) reported that even among these probable AD patients, “most cases are characterized by more or less pronounced vessel alterations” and therefore “we must add this disease pattern to the arteriosclerotic group of senile dementia” (1987 translation, pp. 78-79). These descriptions suggest that senile plaques (drusen) were a common finding in subjects with arteriosclerotic disease.