Affiliations: [a]
Department of Psychology, University of Texas at Austin, Austin, TX, USA
| [b]
Department of Physiology, University of Valencia Faculty of Medicine, Valencia, Spain
Correspondence:
[*]
Correspondence to: Jack C. de la Torre, MD, PhD, Department of Physiology (Hon), University of Valencia Faculty of Medicine, Valencia, Spain. [email protected].
Abstract: This review examines new biomolecular findings that lend support to the hemodynamic role played by chronic brain hypoperfusion (CBH) in driving a pathway to Alzheimer’s disease (AD). CBH is a common clinical feature of AD and the current topic of intense investigation in AD models. CBH is also the basis for the vascular hypothesis of AD which we originally proposed in 1993. New biomolecular findings reveal the interplay of CBH in increasing tau phosphorylation (p-Tau) in the hippocampus and cortex of AD mice, damaging fast axonal transport, increasing signaling of mammalian target of rapamycin (mTOR), impairing learning-memory function, and promoting the formation of neurofibrillary tangles, a neuropathologic hallmark of AD. These pathologic elements have been singularly linked with neurodegeneration and AD but their abnormal, collective participation during brain aging have not been fully examined. The format for this review will provide a consolidated analysis of each pathologic phase contributing to cognitive decline and AD onset, summarized in nine chronological steps. These steps galvanize each factor’s active participation and contribution in constructing a biomolecular pathway to AD onset generated by CBH.
Keywords: Axonal transport, brain hypoperfusion, cognition, mammalian target of rapamycin, neurofibrillary tangles, tau, vascular hypothesis of Alzheimer’s
