Clearance of interstitial fluid (ISF) and CSF (CLIC) group—part of Vascular Professional Interest Area (PIA)

Carare, Roxana O.; Aldea, Roxana; Agarwal, Nivedita; Bacskai, Brian J.; Bechman, Ingo; Boche, Delphine; Bu, Guojun; Bulters, Diederik; Alt, Clemens; Counts, Scott; Leon, Mony J. de; Eide, Per Kristian; Fossati, Silvia; Greenberg, Steven M.; Hamel, Édith; Hawkes, Cheryl A.; Koronyo‐Hamaoui, Maya; Hainsworth, Atticus H.; Holtzman, David M.; Ihara, Masafumi; Jefferson, Angela L.; Kalaria, Raj N.; Kipps, Christopher; Kanninen, Katja M.; Leinonen, Ville; McLaurin, JoAnne; Miners, Scott; Malm, Tarja; Nicoll, James; Piazza, Fabrizio; Paul, Gesine; Rich, Steven M.; Saitô, Satoshi; Shih, Andy Y.; Scholtzova, Henrieta; Snyder, Heather M.; Snyder, Peter J.; Thormodsson, Finnbogi R.; Veluw, Susanne J. van; Weller, Roy O.; Werring, David J.; Wilcock, Donna M.; Wilson, Mark R.; Zloković, Berislav V.; Verma, Ajay

doi:10.1002/dad2.12053

Cited by 54 publications

(50 citation statements)

References 61 publications

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“…In addition, increased apoptosis of the retinal pericytes was found in AD retinas concomitantly with downregulated vascular low-density lipoprotein receptor-related protein 1 (LRP-1), leading to reduced Aβ clearance (Gupta et al, 2020). This was supported by the observation that the accumulation of Aβ in the retina has been closely linked to early loss of pericytes (Carare et al, 2020). These changes have been associated with reduced vascular density.…”

Section: Discussionmentioning

confidence: 92%

A Systematic Review and Meta-Analysis of Retinal Microvascular Features in Alzheimer's Disease

Lei

Ruoxin

et al. 2021

Front. Aging Neurosci.

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Objective: The aim of this meta-analysis was to investigate retinal microvascular features in patients with Alzheimer's disease (AD) using optical coherence tomography angiography (OCTA).Methods: PubMed, Cochrane Library, Embase, and Web of Science databases were systematically searched for published articles comparing retinal microvascular characteristics in subjects with AD and controls. The mean difference (MD) with a 95% confidence interval (CI) was used to assess continuous variables. Review Manager Version (RevMan) 5.30, was employed to analyze the data.Results: Nine studies were included in the meta-analysis. The analysis revealed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in patients with AD than in controls (MD = −1.10, P < 0.0001; MD = −1.61, P = 0.0001, respectively). The value measured by OCTA for parafoveal superficial VD in patients with AD was also remarkably lower than that in the control group (MD = −1.42, P = 0.001), whereas there was no significant difference in the value for parafoveal deep VD (MD = −3.67, P = 0.19), compared to the controls. In addition, the foveal avascular zone (FAZ) was larger in patients with AD than in the control group (MD = 0.08, P = 0.07), although it did not reach statistical significance.Conclusions: The present meta-analysis indicated that the macular whole enface and parafoveal vessel densities were reduced in patients with AD. Moreover, our pooled data revealed that FAZ is larger in patients with AD. Consequently, OCTA may be utilized as a diagnostic tool to identify and monitor patients with AD.

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Section: Discussionmentioning

confidence: 92%

A Systematic Review and Meta-Analysis of Retinal Microvascular Features in Alzheimer's Disease

Lei

Ruoxin

et al. 2021

Front. Aging Neurosci.

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“…In particular, more studies are needed to clarify any possible toxic effects of blood P-tau, especially in conditions in which cerebral vessels are already dysfunctional. On the other hand, CSF Ptau, present at higher concentrations in the perivascular spaces, may be a likely contributor to neurovascular pathology, especially in situations in which perivascular clearance is compromised, which may facilitate its accumulation around brain vessels (85)(86)(87). Interestingly, it has been reported that, besides prompting intracellular toxicity, tau can be secreted and taken up by healthy neurons (88)(89)(90), indicating that extracellular or CSF P-tau may be critical for the progression of tau pathology.…”

Section: Tau and Its Transmissionmentioning

confidence: 99%

Impact of Tau on Neurovascular Pathology in Alzheimer's Disease

Canepa

Fossati

2021

Front. Neurol.

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Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most prevalent cause of dementia. The main cerebral histological hallmarks are represented by parenchymal insoluble deposits of amyloid beta (Aβ plaques) and neurofibrillary tangles (NFT), intracellular filamentous inclusions of tau, a microtubule-associated protein. It is well-established that cerebrovascular dysfunction is an early feature of AD pathology, but the detrimental mechanisms leading to blood vessel impairment and the associated neurovascular deregulation are not fully understood. In 90% of AD cases, Aβ deposition around the brain vasculature, known as cerebral amyloid angiopathy (CAA), alters blood brain barrier (BBB) essential functions. While the effects of vascular Aβ accumulation are better documented, the scientific community has only recently started to consider the impact of tau on neurovascular pathology in AD. Emerging compelling evidence points to transmission of neuronal tau to different brain cells, including astrocytes, as well as to the release of tau into brain interstitial fluids, which may lead to perivascular neurofibrillar tau accumulation and toxicity, affecting vessel architecture, cerebral blood flow (CBF), and vascular permeability. BBB integrity and functionality may therefore be impacted by pathological tau, consequentially accelerating the progression of the disease. Tau aggregates have also been shown to induce mitochondrial damage: it is known that tau impairs mitochondrial localization, distribution and dynamics, alters ATP and reactive oxygen species production, and compromises oxidative phosphorylation systems. In light of this previous knowledge, we postulate that tau can initiate neurovascular pathology in AD through mitochondrial dysregulation. In this review, we will explore the literature investigating tau pathology contribution to the malfunction of the brain vasculature and neurovascular unit, and its association with mitochondrial alterations and caspase activation, in cellular, animal, and human studies of AD and tauopathies.

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“…Mounting evidence indicates that Alzheimer’s Disease (AD) affects the neurosensory retina, a CNS tissue and developmental outgrowth of the diencephalon 1 – 8 . The pathology of AD in the retina appears to mirror the disease in the brain 9 – 16 .…”

Section: Introductionmentioning

confidence: 99%

Color and contrast vision in mouse models of aging and Alzheimer’s disease using a novel visual-stimuli four-arm maze

Vit

Fuchs

Angel

et al. 2021

Sci Rep

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We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensity-controlled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Its application to detect visual impairments during normal aging and over the course of Alzheimer’s disease (AD) is evaluated in wild-type (WT) and transgenic APPSWE/PS1∆E9 murine models of AD (AD+) across an array of irradiance, chromaticity, and contrast conditions. Substantial color and contrast-mode alternation deficits appear in AD+ mice at an age when hippocampal-based memory and learning is still intact. Profiling of timespan, entries and transition patterns between the different arms uncovers variable AD-associated impairments in contrast sensitivity and color discrimination, reminiscent of tritanomalous defects documented in AD patients. Transition deficits are found in aged WT mice in the absence of alternation decline. Overall, ViS4M is a versatile, controlled device to measure color and contrast-related vision in aged and diseased mice.

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Clearance of interstitial fluid (ISF) and CSF (CLIC) group—part of Vascular Professional Interest Area (PIA)

Cited by 54 publications

References 61 publications

A Systematic Review and Meta-Analysis of Retinal Microvascular Features in Alzheimer's Disease

A Systematic Review and Meta-Analysis of Retinal Microvascular Features in Alzheimer's Disease

Impact of Tau on Neurovascular Pathology in Alzheimer's Disease

Color and contrast vision in mouse models of aging and Alzheimer’s disease using a novel visual-stimuli four-arm maze

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