scholarly journals Fungicide Exposure and Amyloid Plaques in Mice: Further Evidence of an Environmental Risk Factor for Alzheimer’s Disease

2020 ◽  
Vol 128 (9) ◽  
pp. 094006
Author(s):  
Silke Schmidt
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Environmental Risk ◽  
Amyloid Plaques ◽  
Environmental Risk Factor

scholarly journals Dysregulation of Hypothalamic-Pituitary-Adrenal (HPA) Axis in Alzheimer’s Disease and use of Non Selective and Selective Glucocorticoid Receptor Modulators to Improve Cognitive function – Review of Literature

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Hpa Axis ◽  
Memory Loss ◽  
Environmental Risk Factor ◽  
Review Of Literature ◽  
Hypothalamic Pituitary Adrenal ◽  
Potential Therapeutic Role ◽  
Receptor Modulators

Alzheimer's disease (AD) is a relentless neurodegenerative disease affecting more than 36 million people worldwide. Increased evidence suggests stress and its synonymous elevated circulating glucocorticoid levels, due to dysregulation of Hypothalamic-Pituitary-Adrenal (HPA) axis, is an important environmental risk factor for the onset and progression of AD [1]. Here we review recent data on the effect of glucocorticoids on spontaneous activity of HPA axis with particular emphasis on AD, and how modulation of glucocorticoid (GC) levels or GC receptors (GCRs) could potentially mediate disease processes. Early phase of AD is characterized by hippocampal memory (episodic memory) loss and impaired synaptic plasticity [2]. In a study at IPMC in France on mouse model AD, treatment with GCR antagonist, mifepristone (RU486) reduced cerebral B Amyloid (AB), Tau pathologies and cognitive impairment [3]. Pointing to a potential therapeutic role for interventions to underlying HPA axis and GCRs activity.

Vascular and mixed dementia

2020 ◽  
pp. 479-494
Author(s):  
Robert Stewart
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Controlled Trial ◽  
Diagnostic System ◽  
Research Area ◽  
Healthy Lifestyles ◽  
Environmental Risk Factor ◽  
Trial Evidence

Vascular disease is the most important environmental risk factor for dementia but this research area has been hampered by inadequate outcome definitions—in particular, a diagnostic system that attempts to separate overlapping and probably interacting pathologies. There is now substantial evidence that the well-recognized risk factors for cardiovascular disease and stroke are also risk factors for dementia, including Alzheimer’s disease. However, these risk factors frequently act over several decades, meaning that the chances of definitive randomized controlled trial evidence for risk-modifying interventions are slim. This should not obscure the wide opportunity for delaying or preventing dementia through risk factor control and uncontroversial healthy lifestyles. Care should also be taken that comorbid cerebrovascular disease is not considered as excluding a diagnosis of Alzheimer’s disease, particularly now that this determines treatment eligibility.

Liberation of Copper from Amyloid Plaques: Making a Risk Factor Useful for Alzheimer’s Disease Treatment

2012 ◽  
Vol 55 (21) ◽  
pp. 9146-9155 ◽  
Author(s):  
Jie Geng ◽  
Meng Li ◽  
Li Wu ◽  
Jinsong Ren ◽  
Xiaogang Qu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Amyloid Plaques ◽  
Disease Treatment

Repurposing Antihypertensive Drugs for the Management of Alzheimer’s Disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Keng Yoon Yeong ◽  
Christine Law
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Literature Review ◽  
Neurodegenerative Disorder ◽  
Antihypertensive Drugs ◽  
Future Prospects ◽  
Short Term

Alzheimer’s disease (AD) is a neurodegenerative disorder that has affected millions of people worldwide. However, currently there is no treatment to cure the disease. The AD drugs available in the market only manage the disease symptomatically and the effects are usually short-term. Thus, there is a need to look at alternatives AD therapies. Mid-life hypertension has not only been recognised as a risk factor for AD, but its relation with AD has also been well established. Thus, antihypertensives are postulated to be beneficial in managing AD. This literature review aims to shed some light on the potential of repurposing antihypertensives to treat AD, considering recent updates. Four classes of antihypertensives, as well as their potential limitations and future prospects in being utilised as AD therapeutics are discussed in this review.

Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

2019 ◽  
Vol 16 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Alexander Sturzu ◽  
Sumbla Sheikh ◽  
Hubert Kalbacher ◽  
Thomas Nägele ◽  
Christopher Weidenmaier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Flow Cytometry ◽  
Transgenic Mice ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Laser Scanning Microscopy ◽  
Β Amyloid ◽  
Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

scholarly journals Interactions between sleep disturbances and Alzheimer’s disease on brain function: a preliminary study combining the static and dynamic functional MRI

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kaicheng Li ◽  
Xiao Luo ◽  
Qingze Zeng ◽  
Yerfan Jiaerken ◽  
Shuyue Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Sleep Disturbance ◽  
Brain Function ◽  
Sleep Disturbances ◽  
Brain Activity ◽  
Vascular Risk Factor ◽  
Underlying Mechanism ◽  
Amyloid Pet

AbstractThough sleep disturbance constitutes the risk factor for Alzheimer’s disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.

scholarly journals In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eugene Kim ◽  
Davide Di Censo ◽  
Mattia Baraldo ◽  
Camilla Simmons ◽  
Ilaria Rosa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
Transgenic Animals ◽  
Surrounding Tissue ◽  
Rodent Models ◽  
Enhanced Mri ◽  
5Xfad Mice ◽  
Manganese Enhanced Mri

AbstractAmyloid plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Animals were given subcutaneous injections of MnCl2 and imaged in vivo using a 9.4 T Bruker scanner. MnCl2 improved signal-to-noise ratio but was not necessary to detect plaques in high-resolution images. Plaques were visible in all transgenic animals and no wild-types, and quantitative susceptibility mapping showed that they were more paramagnetic than the surrounding tissue. This, combined with beta-amyloid and iron staining, indicate that plaque MR visibility in both animal models was driven by plaque size and iron load. Longitudinal relaxation rate mapping revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. This was limited to the rhinencephalon in the TgF344-AD rats, while it was most significantly increased in the cortex of the 5xFAD mice. Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats. Multi-parametric MEMRI is a simple, viable method for detecting amyloid plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present the first in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.

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