Cerebrovascular phenotypes in mouse models of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a devastating neurological degenerative disorder and is the most common cause of dementia in the elderly. Clinically, AD manifests with memory and cognitive decline associated with deposition of hallmark amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although the mechanisms underlying AD remains unclear, two hypotheses have been proposed. The established amyloid hypothesis states that Aβ accumulation is the basis of AD and leads to formation of NFTs. In contrast, the two-hit vascular hypothesis suggests that early vascular damage leads to increased accumulation of Aβ deposits in the brain. Multiple studies have reported significant morphological changes of the cerebrovasculature which can result in severe functional deficits. In this review, we delve into known structural and functional vascular alterations in various mouse models of AD and the cellular and molecular constituents that influence these changes to further disease progression. Many studies shed light on the direct impact of Aβ on the cerebrovasculature and how it is disrupted during the progression of AD. However, more research directed towards an improved understanding of how the cerebrovasculature is modified over the time course of AD is needed prior to developing future interventional strategies.

Large scale in vivo acquisition, segmentation, and 3D reconstruction of cortical vasculature using open-source functional ultrasound imaging platform

“…Several strategies are now allowing for longitudinal monitoring of the brain functions of the same animal which in this context would be of high interest when considering pathologies as the brain vasculature and the associated functions have been shown affected (e.g., angiogenesis, vascular rarefaction, hypertension) in various diseases including Alzheimer’s (Meyer et al, 2008; Gutierrez et al, 2016; Zhang et al, 2019; Lowerison et al, 2021; Szu and Obenaus, 2021) and Parkinson’s diseases (Yang et al, 2015; Al-Bachari et al, 2020; Biju et al, 2020), tumors (Gambarota et al, 2008; Guyon et al, 2021), obesity (Dorrance et al, 2014; Pétrault et al, 2019; Gruber et al, 2021) currently addressed at the brain-wide scale with either technology offering reduced spatiotemporal resolution (Pathak et al, 2011; Lin et al, 2013) or post-mortem strategies (Hlushchuk et al, 2020; Todorov et al, 2020; Bumgarner and Nelson, 2022). In the stroke context, the cortex-wide skeletonization of vessels could also be used as a follow-up strategy for detecting i) progressive and long-lasting neovascularization of the infarcted tissue (Ergul et al, 2012; Liman and Endres, 2012), and ii) stroke-induced of reverse flow (Li et al, 2010; Ergul et al, 2012) both of crucial interest when considering tissue survival and functional recovery of the insulted tissue.…”

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

“…Blood flow reductions have also been identified in early preclinical AD, before Aβ plaque deposition (Nicolakakis and Hamel, 2011;Iturria-Medina et al, 2016;Szu and Obenaus, 2021).…”

Blood–brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders

“…4 ) [ 93 ]. The hyperphosphorylated tau neurofibrillary tangles (NFTs), Aβ plaques, neuronal loss, and cerebrovascular dysfunction are majorly proposed to contribute to AD pathophysiology and cognitive impairment [ 94 ]. NFTs caused by the accumulation of phosphorylated tau protein in the neuron can also lead to AD which is associated with chromosome no.…”