Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer’s disease

Ni, Ruiqing; Rudin, Markus; Klohs, Jan

doi:10.1016/j.pacs.2018.04.001

Cited by 57 publications

(59 citation statements)

References 57 publications

(75 reference statements)

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“…Studies in animal models of cerebral amyloidosis have reported age-dependent reductions in rCBF ( Fig. 3b) [46,[49][50][51][82][83][84]. Interestingly, hyperperfusion was found in the rTG4510 mouse model of tauopathy [85], but have so far not been reported for models of cerebral amyloidosis.…”

Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 95%

“…Studies in animal models of AD collectively reported hypoperfusion in animal models of cerebral amyloidosis [46,[49][50][51][82][83][84]. The reductions in rCBF have been found to be age-dependent ( Fig.…”

Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 95%

“…Vascular remodelling has been also described to occur in animal models of cerebral amyloidosis [46][47][48], where some of the strains also display CAA [24,31,47,[49][50][51]. A recent study described changes in vessel den-sity and morphology in a transgenic model of tauopathy [52].…”

Section: The Interplay Between Vascular Remodelling and Cerebral Hemomentioning

confidence: 99%

“…3b) [50,51,82], and to Neurodegener Dis 2019;19:109-127 DOI: 10.1159/000505625 occur prior to cerebral Aβ deposition [49]. Reductions in rCBF have been found in strains with neurodegeneration and brain atrophy [86], but also in models that do not have this phenotype [46,50,51]. Hypoperfusion has been attributed to an impaired vascular regulation by soluble Aβ [87].…”

Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 99%

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An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

Klohs

2019

Neurodegener Dis

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Background: Cerebrovascular disease is a common comorbidity in patients with Alzheimer's disease (AD). It is believed to contribute additively to the cognitive impairment and to lower the threshold for the development of dementia. However, accumulating evidence suggests that dysfunction of the cerebral vasculature and AD neuropathology interact in multiple ways. Vascular processes even proceed AD neuropathology, implicating a causal role in the etiology of AD. Thus, the review aims to provide an integrated view on vascular dysfunction in AD. Summary: In AD, the cerebral vasculature undergoes pronounced cellular, morphological and structural changes, which alters regulation of blood flow, vascular fluid dynamics and vessel integrity. Stiffening of central blood vessels lead to transmission of excessive pulsatile energy to the brain microvasculature, causing endorgan damage. Moreover, a dysregulated hemostasis and chronic vascular inflammation further impede vascular function, where its mediators interact synergistically. Changes of the cerebral vasculature are triggered and driven by systemic vascular abnormalities that are part of aging, and which can be accelerated and aggravated by cardiovascular diseas-es. Key Messages: In AD, the cerebral vasculature is the locus where multiple pathogenic processes converge and contribute to cognitive impairment. Understanding the molecular mechanism and pathophysiology of vascular dysfunction in AD and use of vascular blood-based and imaging biomarker in clinical studies may hold promise for future prevention and therapy of the disease.

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Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 95%

Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 95%

Section: The Interplay Between Vascular Remodelling and Cerebral Hemomentioning

confidence: 99%

Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 99%

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An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

Klohs

2019

Neurodegener Dis

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“…Thus, in the future novel probes may be developed and tested, which show better correspondence with true Aβ plaque size (27). APP/PS1 is a widely used animal model for AD mechanistic study (62)(63)(64)(65)(66). The single Adeposits detection described in the current work is directly applicable to study A plaque clearance (67)(68)(69)(70), and to monitor antibody treatment effect in the mouse models (9,62,71,72), which can currently only be achieved by craniotomy and ex vivo techniques.…”

Section: Discussionmentioning

confidence: 99%

Transcranial in vivo detection of amyloid-beta at single plaque resolution with large-field multifocal illumination fluorescence microscopy

Chen²,

Shi³

et al. 2020

Preprint

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The abnormal deposition of beta-amyloid proteins in the brain is one of the major histopathological hallmarks of Alzheimer's disease. Currently available intravital microscopy techniques for highresolution plaque visualization commonly involve highly invasive procedures and are limited to a small field-of-view within the rodent brain. Here, we report the transcranial detection of amyloidbeta deposits at the whole brain scale with 20 m resolution in APP/PS1 and arcA mouse models of Alzheimer's disease amyloidosis using a large-field multifocal (LMI) fluorescence microscopy technique. Highly sensitive and specific detection of amyloid-beta deposits at a single plaque level in APP/PS1 and arcA mice was facilitated using luminescent conjugated oligothiophene HS-169.Immunohistochemical staining with HS-169, anti-A antibody 6E10, and conformation antibodies OC (fibrillar) of brain tissue sections further showed that HS-169 resolved compact parenchymal and vessel-associated amyloid deposits. The novel imaging platform offers new prospects for in vivo studies into Alzheimer's disease mechanisms in animal models as well as longitudinal monitoring of therapeutic responses at a single plaque level.

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Optical imaging technology realizes early tumor diagnosis by detecting angiogenesis

Han

2022

Microscopy Res & Technique

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The occurrence and development of blood vessels play a key role in different stages of tumor growth, while current imaging techniques are difficult to detect early tumor angiogenesis because of their low sensitivity. Therefore, this article introduces highsensitivity optical imaging technology to achieve early tumor diagnosis by detecting tumor angiogenesis. Liver and pancreatic tumor models in nude mice were respectively established to represent tumors with a rich or poor blood supply. The two optical imaging methods, in vivo confocal fluorescence imaging and photoacoustic imaging, were used to detect tumor angiogenesis at different stages. Finally, the changes in blood vessels were verified by immunostaining. Both autoluminescence imaging and pathological staining confirmed that these two tumor models were successfully established.In vivo confocal fluorescence imaging found that the early tumor blood vessel structure had obvious characteristics: disorder, tortuous deformation, thin diameter, which were significantly different from the normal tissues. Photoacoustic imaging could effectively identify blood vessels inside early tumors, which were small and disordered and might be used as one of the predictors of early tumor development. CD31 immunostaining was used to evaluate the vascular status of tumors at different stages and under different blood supply conditions. The vascular structures observed under the microscope in the two tumor models were consistent with the results observed by optical imaging methods. The optical imaging methods could monitor the characteristics of angiogenesis in the rich or poor blood supply tumors, especially the early diagnosis of tumors.

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Cortical hypoperfusion and reduced cerebral metabolic rate of oxygen in the arcAβ mouse model of Alzheimer’s disease

Cited by 57 publications

References 57 publications

An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

Transcranial in vivo detection of amyloid-beta at single plaque resolution with large-field multifocal illumination fluorescence microscopy

Optical imaging technology realizes early tumor diagnosis by detecting angiogenesis

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