The Neurovasculome: Key Roles in Brain Health and Cognitive Impairment: A Scientific Statement From the American Heart Association/American Stroke Association

Abstract

BACKGROUND: Preservation of brain health has emerged as a leading public health priority for the aging world population. Advances in neurovascular biology have revealed an intricate relationship among brain cells, meninges, and the hematic and lymphatic vasculature (the neurovasculome) that is highly relevant to the maintenance of cognitive function. In this scientific statement, a multidisciplinary team of experts examines these advances, assesses their relevance to brain health and disease, identifies knowledge gaps, and provides future directions. METHODS: Authors with relevant expertise were selected in accordance with the American Heart Association conflict-of-interest management policy. They were assigned topics pertaining to their areas of expertise, reviewed the literature, and summarized the available data. RESULTS: The neurovasculome, composed of extracranial, intracranial, and meningeal vessels, as well as lymphatics and associated cells, subserves critical homeostatic functions vital for brain health. These include delivering O 2 and nutrients through blood flow and regulating immune trafficking, as well as clearing pathogenic proteins through perivascular spaces and dural lymphatics. Single-cell omics technologies have unveiled an unprecedented molecular heterogeneity in the cellular components of the neurovasculome and have identified novel reciprocal interactions with brain cells. The evidence suggests a previously unappreciated diversity of the pathogenic mechanisms by which disruption of the neurovasculome contributes to cognitive dysfunction in neurovascular and neurodegenerative diseases, providing new opportunities for the prevention, recognition, and treatment of these conditions. CONCLUSIONS: These advances shed new light on the symbiotic relationship between the brain and its vessels and promise to provide new diagnostic and therapeutic approaches for brain disorders associated with cognitive dysfunction.

Mechanisms linking cerebrovascular dysfunction and tauopathy: Adding a layer of epiregulatory complexity

“…Tau pathology-induced activation of glial cells stimulates the trafficking of immune cells across the BBB (Figure 1), which overtime is detrimental (Blair et al, 2015;Chen et al, 2023;Majerova et al, 2019). Although correlative studies support an association of activated innate and adaptive immune cells with cognitive dysfunction, animal studies have suggested a clear cause-effect relationship between increased immune cell trafficking to the brain and cognitive decline (Iadecola, 2023).…”

“…Furthermore, the recent discovery that central nervous system antigens accumulate in dural sinuses and are presented to circulating lymphocytes, a process disrupted during neuroinflammatory states and ageing, supports and alteration of the cross-talk between the central nervous system and systemic immunity in the disease process (Iadecola, 2023;Rustenhoven, 2021). In addition, tau pathological species, through astrocytic end-feet and interstitial fluids, may spread to endothelial cells and pericytes, inducing BBB disruption and permeability to blood-borne components, including peripheral blood monocyte-derived macrophages, immunoglubulins (IgGs and IgMs) and α2-macroglobulin (Figure 1) (Canepa & Fossati, 2020).…”

Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?

“…Together, these cellular and acellular elements form the NVU responsible for maintaining the homeostasis and function of the brain microenvironment by synchronizing the energetic demand with vasodynamic changes. The NVU composition differs depending upon location within the cerebrovascular network [28,29].…”

Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance

“…Adropin is neurotrophic when applied directly to cultured neurons 14 , while also preserving cerebrovascular function in situations of ischemia [19][20][21][22] . Adropin could thus support synaptic plasticity in the brain while also preventing neurovascular diseases thought to contribute to cognitive decline 23 . However, whether the results from mouse studies are translatable to the human condition has not been determined.…”