Biomarkers Assessing Endothelial Dysfunction in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common degenerative disorder in the elderly in developed countries. Currently, growing evidence is pointing at endothelial dysfunction as a key player in the cognitive decline course of AD. As a main component of the blood–brain barrier (BBB), the dysfunction of endothelial cells driven by vascular risk factors associated with AD allows the passage of toxic substances to the cerebral parenchyma, producing chronic hypoperfusion that eventually causes an inflammatory and neurotoxic response. In this process, the levels of several biomarkers are disrupted, such as an increase in adhesion molecules that allow the passage of leukocytes to the cerebral parenchyma, increasing the permeability of the BBB; moreover, other vascular players, including endothelin-1, also mediate artery inflammation. As a consequence of the disruption of the BBB, a progressive neuroinflammatory response is produced that, added to the astrogliosis, eventually triggers neuronal degeneration (possibly responsible for cognitive deterioration). Recently, new molecules have been proposed as early biomarkers for endothelial dysfunction that can constitute new therapeutic targets as well as early diagnostic and prognostic markers for AD.

Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study

“…Moreover, we expect that COVID-19 infection will lead to an elevation in circulating reactive oxygen species (ROS), proinflammatory cytokines, and biomarkers of endothelial dysfunction. Elevation in these molecules have a deleterious effect on the vasculature [ 91 ] and is implicated in the development of cognitive decline and dementia [ 103 , 109 ]. Furthermore, evidence suggests that following recovery of COVID-19 infection, there is a prolonged thromboinflammatory response, in part, mediated by systemic endothelial dysfunction [ 106 ].…”

“…Growing evidence points towards endothelial impairment as a key mediator in the progression from cognitive decline to dementia. Molecules represented in the cardiovascular disease panel have been reported as biomarkers of endothelial dysfunction in vascular diseases [ 102 ] and dementia [ 103 ]. Additionally, higher levels VCAM-1 and ICAM-1 were able to differentiate AD vs MCI [ 104 ].…”

Advances in nanoprobes for molecular MRI of Alzheimer's disease

“…This allows nanoparticles to "leak" passively into the brain. Studies have also shown that the proinflammatory microenvironment in AD brain results in an inflamed endothelium that expresses elevated levels of cell adhesion molecules, including VCAM-1, ICAM-1, and P-selectin (Custodia et al, 2023;Grammas, 2011;Tarawneh et al, 2022;Zhang & Mao, 2020). Nanoprobes targeting overexpressed cell surface receptors can be exploited for trafficking imaging reporters into the brain.…”

The Critical Role of Biomarkers for Drug Development Targeting the Biology of Aging

“…A postmortem study estimated that approximately 80% of people with AD have vascular pathology (55). Extensive research has shown that vascular impairment leads to reduced cerebral blood flow, endothelial damage, BBB leakage, demyelination, and cerebral atrophy, all of which can contribute to AD pathology and clinical decline (56,57).…”