Cerebral Hypoperfusion, Capillary Degeneration, and Development of Alzheimer Disease

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Abstract
Considerable clinical and experimental data have shown that cerebral perfusion is progressively decreased during increased aging and that this decrease in brain blood flow is significantly greater in Alzheimer disease (AD). The authors propose that advanced aging with a comorbid condition, such as a vascular risk factor, which further decreases cerebral perfusion, promotes a critically attained threshold of cerebral hypoperfusion (CATCH). With time, CATCH induces brain capillary degeneration and suboptimal delivery of energy substrates to neuronal tissue. Because glucose is the main fuel of brain cells, its impaired delivery, with the deficient delivery of oxygen, compromises neuronal stability because the supply for aerobic glycolysis fails to meet brain tissue demand. The outcome of CATCH is a metabolic cascade that involves, among other things, mitochondrial dysfunction, oxidative stress, decreased adenosine triphosphate production, abnormal protein synthesis, cell ionic pump deficiency, signal transduction defects, and neurotransmission failure. These events contribute to the progressive cognitive decline characteristic of patients with AD, as well as regional anatomic pathology, consisting of synaptic loss, senile plaques, neurofibrillary tangles, tissue atrophy, and neurodegeneration. CATCH identifies the clinical heterogeneic pattern that characterizes AD because it provides compelling evidence that any of a multitude of different etiopathophysiologic vascular risk factors, in the presence of advanced aging, can lead to AD. The evidence in support of CATCH as the pathogenic trigger of AD is crystallized in this review.