A Novel Transgenic Rat Model of Robust Cerebral Microvascular Amyloid with Prominent Vasculopathy.

A Novel Transgenic Rat Model of Robust Cerebral Microvascular Amyloid with Prominent Vasculopathy. Am J Pathol. 2018 Nov 10;: Authors: Davis J, Xu F, Hatfield J, Lee H, Hoos MD, Popescu D, Crooks E, Kim R, Smith SO, Robinson JK, Benveniste H, Van Nostrand WE Abstract Accumulation of fibrillar amyloid β protein in blood vessels of the brain, a condition known as cerebral amyloid angiopathy (CAA), is a common pathology of elderly individuals, a prominent comorbidity of Alzheimer disease, and a driver of vascular cognitive impairment and dementia. Although several transgenic mouse strains have been generated that develop varying levels of CAA, consistent models of associated cerebral microhemorrhage and vasculopathy observed clinically have been lacking. Reliable preclinical animal models of CAA and microhemorrhage are needed to investigate the molecular pathogenesis of this condition. Herein, we describe the generation and characterization of a novel transgenic rat (rTg-DI) that produces low levels of human familial CAA Dutch/Iowa E22Q/D23N mutant amyloid β protein in brain and faithfully recapitulates many of the pathologic aspects of human small-vessel CAA. rTg-DI rats exhibit early-onset and progressive accumulation of cerebral microvascular fibrillar amyloid accompanied by early-onset and sustained behavioral deficits. Comparable to CAA in humans, the cerebral microvascular amyloid in rTg-DI rats causes capillary structural alterations, promo...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research

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Magnetic resonance imaging (MRI) of the brain allows for the identification of structural lesions typical of Alzheimer's disease (AD), the main cause of dementia. However, to have a clinical impact, it is imperative that acquisition and reporting of this MRI-based evidence be standardized, ensuring the highest possible reliability and reproducibility. Our objective was to validate a systematic radiological MRI acquisition and review process in the context of AD.
Source: Canadian Association of Radiologists Journal - Category: Radiology Authors: Tags: Magnetic Resonance Imaging / Formation image de r ésonance magnétique Source Type: research
This study aimed to investigate the association between cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), amyloid- and 18F-FDG positron emission tomography (PET) measures at baseline, in relation to cognitive changes and conversion to AD dementia over a short-term (12-month) period. We included 13 healthy controls, 49 MCI and 16AD dementia patients with a clinical-based diagnosis and a complete A/T/N characterization at baseline. Global cortical amyloid-β (Aβ) burden was quantified using the 18F-AV45 standardized uptake value ratio (SUVR) with two different reference regions (cerebellar grey and subcor...
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
ConclusionsThis study provides a tentative indication that quantitative tract-specific microstructural WM abnormalities, but not quantitative functional connectivity of the DMN, may aid early-stage and follow-up differential diagnosis of bvFTD and AD. Specifically, pronounced microstructural changes in anterior WM tracts may characterise bvFTD, whereas microstructural abnormalities of the hippocampal cingulum may characterise AD.Key Points• The clinical applicability of quantitative brain imaging measures for early-stage and follow-up differential diagnosis of dementia subtypes was explored using a group-wise approach...
Source: European Radiology - Category: Radiology Source Type: research
Publication date: Available online 4 March 2019Source: NeuroImageAuthor(s): Răzvan V. Marinescu, Arman Eshaghi, Marco Lorenzi, Alexandra L. Young, Neil P. Oxtoby, Sara Garbarino, Sebastian J. Crutch, Daniel C. Alexander, for the Alzheimer's Disease Neuroimaging InitiativeAbstractCurrent models of progression in neurodegenerative diseases use neuroimaging measures that are averaged across pre-defined regions of interest (ROIs). Such models are unable to recover fine details of atrophy patterns; they tend to impose an assumption of strong spatial correlation within each ROI and no correlation among ROIs. Such assumptions ma...
Source: NeuroImage - Category: Neuroscience Source Type: research
AbstractInflammaging describes the complexity between low-grade chronic inflammation with the pathogenesis of brain aging and Alzheimer ´s disease (AD). We aimed to find associations of inflammatory markers: i) white blood cell count (WBC), ii) high-sensitivity C-reactive protein (hs-CRP), and iii) fibrinogen with brain structures, sensitive neuroimaging markers of advanced brain aging and AD-like atrophy, and cognitive aging score s. We analyzed magnetic resonance imaging (MRI) scans of 2204 participants from the Study of Health in Pomerania-2 (SHIP-2) and SHIP-Trend (55.6% women, mean age 52.4±13.7 years). A...
Source: Brain Imaging and Behavior - Category: Neurology Source Type: research
This study aimed to examine short-term reliability of the default-mode network (DMN), one of the main haemodynamic patterns of the brain.Materials and methodsUsing a 1.5 T Philips Achieva scanner, two consecutive resting-state fMRI runs were acquired on 69 healthy adults, 62 patients with mild cognitive impairment (MCI) due to AD, and 28 patients with AD dementia. The anterior and posterior DMN and, as control, the visual-processing network (VPN) were computed using two different methodologies: connectivity of predetermined seeds (theory-driven) and dual regression (data-driven). Divergence and convergence in network stren...
Source: Magnetic Resonance Materials in Physics, Biology and Medicine - Category: Materials Science Source Type: research
This study aimed to examine short-term reliability of the default-mode network (DMN), one of the main haemodynamic patterns of the brain. MATERIALS AND METHODS: Using a 1.5 T Philips Achieva scanner, two consecutive resting-state fMRI runs were acquired on 69 healthy adults, 62 patients with mild cognitive impairment (MCI) due to AD, and 28 patients with AD dementia. The anterior and posterior DMN and, as control, the visual-processing network (VPN) were computed using two different methodologies: connectivity of predetermined seeds (theory-driven) and dual regression (data-driven). Divergence and convergence in netwo...
Source: Magma - Category: Radiology Authors: Tags: MAGMA Source Type: research
Conclusion: Our findings suggest that MM imaging could be a clinically proper modality to estimate the myelination changes in AD patients.Dement Geriatr Cogn Disord Extra 2019;9:24 –33
Source: Dementia and Geriatric Cognitive Disorders Extra - Category: Geriatrics Source Type: research
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Source: NeuroImage: Clinical - Category: Radiology Source Type: research
In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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