Preprint Review Version 1 This version is not peer-reviewed

Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease

Version 1 : Received: 3 September 2024 / Approved: 3 September 2024 / Online: 3 September 2024 (16:58:12 CEST)

How to cite: Hayden, M. R. Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease. Preprints 2024, 2024090259. https://doi.org/10.20944/preprints202409.0259.v1 Hayden, M. R. Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease. Preprints 2024, 2024090259. https://doi.org/10.20944/preprints202409.0259.v1

Abstract

The microvessel neurovascular unit with its brain endothelial cell (BEC) and blood-brain barrier remodeling is important in the development of impaired cognition in sporadic or late-onset Alzheimer’s disease (LOAD) and vascular dementia or vascular cognitive impairment and dementia including cerebral amyloid angiopathy in neurodegeneration. LOAD is considered to be the number one cause of dementia globally; however, when one considers the role of mixed dementia (MD) (the combination of both the amyloid cascade hypothesis and the vascular hypothesis of LOAD), it becomes apparent that MD is the number one cause. The microvessel BECs are the first cells in the brain to be exposed to the peripheral neurotoxins of the systemic circulation and are therefore the brain cells at the highest risk for early and chronic injury. Therefore, it is not surprising that microvessel BECs are the first cells to undergo injury and the response to injury wound healing mechanism and remodeling that is excessive and recurrent in the aging process plus other age-related diseases such as cerebro-cardiovascular disease, hypertension, type 2 diabetes mellitus, Parkinson’s disease, plus others. This narrative review explores the intricate relationship between microvessel remodeling, cerebral small vessel disease (SVD), and neurodegeneration as occurs in LOAD. Further, it discusses the current understanding of how microvessel dysfunction, disruption, and pathology contribute to the pathogenesis of LOAD and thus, highlights potential avenues for therapeutic interventions.

Keywords

Brain endothelial cells; Blood-brain barrier; Dementia; Late-onset Alzheimer's disease; Microvessel remodeling; Neurodegeneration; Neurovascular unit; Small vessel disease

Subject

Biology and Life Sciences, Neuroscience and Neurology

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