The Animal Models of Dementia and Alzheimer’s Disease for Pre-Clinical Testing and Clinical Translation

Anand, Akshay; Banik, Avijit; Thakur, Keshav; Masters, Colin L.

doi:10.2174/156720512803569055

Cited by 40 publications

(32 citation statements)

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“…Experimental models of AD rely on the expression of rare human familial mutations and often develop Aβ pathology due to an overproduction of Aβ peptides, rather than a failure of endogenous clearance mechanisms 10. Furthermore, histopathologic findings characteristic for CSVD are missing in most AD models and inbred-provoked uniformity of animals does not adequately address the heterogeneity of human disease 11…”

Section: Introductionmentioning

confidence: 99%

“…Experimental models of AD rely on the expression of rare human familial mutations and often develop Ab pathology due to an overproduction of Ab peptides, rather than a failure of endogenous clearance mechanisms. 10 Furthermore, histopathologic findings characteristic for CSVD are missing in most AD models and inbred-provoked uniformity of animals does not adequately address the heterogeneity of human disease. 11 In contrast to the broader assortment of experimental AD models, there are several available CSVD models generated by either (1) the induction of local and global hypoperfusion, (2) transgenic modifications leading to vasoconstrictions of cerebral arteries and small vessel wall damage, and by (3) provoked chronic hypertension.…”

Section: Introductionmentioning

confidence: 99%

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Hypertension drives parenchymal β‐amyloid accumulation in the brain parenchyma

Bueche

Hawkes

Garz

et al. 2014

Ann Clin Transl Neurol

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There is substantial controversy regarding the causative role of amyloid β (Aβ) deposition in Alzheimer's disease (AD). The cerebrovasculature plays an important role in the elimination of Aβ from the brain and hypertension is a well-known risk factor for AD. In spontaneously hypertensive stroke-prone rats (SHRSP), an animal model of chronic arterial hypertension, cerebral small vessel disease (CSVD) leads to age-dependent parenchymal Aβ accumulation similar to that observed in AD. These data approve the neuropathological link between CSVD and AD, confirm the challenge that parenchymal Aβ deposition is a specific marker for AD and disclose the meaning of SHRSP as valid experimental model to investigate the association between hypertension, CSVD, and Aβ plaques.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypertension drives parenchymal β‐amyloid accumulation in the brain parenchyma

Bueche

Hawkes

Garz

et al. 2014

Ann Clin Transl Neurol

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show abstract

“…Among these, rats and mice are widely used, and their transgenic counterparts are the most-established system to evaluate disease pathophysiology as well as effective treatment strategies. Several strategies have been adopted to establish AD like pathologies and induced memory impairment in these models [33]. These include predetermined brain injury, neurotoxin induced cell loss in brain and intra-cerebroventricular injection of Aβ peptides [34].…”

Section: Pre-clinical Studies To Probe Regenerative Potential Of Stemmentioning

confidence: 99%

Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?

Bali¹,

Lahiri²,

Banik³

et al. 2017

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Alzheimer’s disease (AD) is one of the most common causes of dementia. Despite several decades of serious research in AD there is no standard disease modifying therapy available. Stem cells hold immense potential to regenerate tissue systems and are studied in a number of brain-related disorders. For various untreatable neurodegenerative disorders, such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) (current-approved drugs provide only symptomatic relief), stem cell therapy holds a great promise and provides a great research opportunity. Here we review several stem cell transplantation studies with reference to both preclinical and clinical approaches. We focus on different sources of stem cells in a number of animal models and on molecular mechanisms involved in possible treatment of neurodegenerative disorders. The clinical studies reviewed suggest safety efficacy and translational potential of stem cell therapy. The therapeutic outcome of stem cell transplantation has been promising in many studies but no unifying hypothesis exists for an underlying mechanism. Some studies reported paracrine effects exerted by these cells via release of neurotrophic factors, while other studies reported immunomodulatory effects by transplanted cells. There are also reports supporting stem cell transplantation causing endogenous cell proliferation or replacement of diseased cells at the site of degeneration. In animal models of AD, stem cell transplantation is also believed to increase expression of synaptic proteins. A number of stem cell transplantation studies point out great potential for this novel approach in preventing or halting several neurodegenerative diseases. The current challenge is to clearly define the molecular mechanism by which stem cells operate and the extent of actual contribution by the exogenous and/or endogenous cells in the rescue of disease.

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“…On the other side, diverse kind of targets could be good options for blocking the progression of brain impairment and dementia (Anand et al, 2012), but this raises difficult questions like; How to define the stem event, Temporal sequence of the neurodegenerative processes, Sex and age dependent effects, when and how to carry out the intervention as well as the best analog situation in humans for a better safety and efficacy properties?…”

Section: Preclinical Studies and Molecular Targetsmentioning

confidence: 99%

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

Cardona‐Gómez

Lopera

2016

Front. Aging Neurosci.

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Latin-American people with dementia will increase to an astounding 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type like Alzheimer, and vascular dementia (VaD) progression after Cerebrovascular disease is also found. These incidences are increased in Colombia by specific populations affected with pure Neurodegenerative and VaDs like Autosomical Dominant familial Alzheimer’s disease (AD) and Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). In spite of the enormous human effort with and economical effort and investment costs, neither sporadic nor genetic kinds of dementia progression have been prevented or blocked yet. Currently, there exist several animal models that partially solve the understanding of the neurodegenerative etiopathogenesis and its treatment. However, when the potential therapies are translated to humans, those do not work or present a limited action. Main difficulties are the diverse comorbility associated to the cause and/or several affected brain regions, reducing the efficacy of some therapies which are limited to a tissue-specific action or modulating a kind of neurotransmission. Global investigation suggests that a general prevention could be achieved with the improvement in the quality of lifestyle, including healthy diet, physical and mental activity, and avoiding mechanical or chemical pro-inflammatory events in an early stage in the most of non-communicable diseases. In this review article, we present some molecular targets and preclinical studies in animal models to propose strategies that could be useful in a future translation to prevent or block neurodegeneration: one is gene therapy; silencing pathogenic genes in critical brain areas where excitotoxicity arise and spread. Another is to take advantage of the natural source and its wide biodiversity of natural products that are capable of identifying, by the blocking and prevention of neurodegeneration. On the other side, the casuistic of pure dementias in the Latin-American region gives an exceptional opportunity to understand the pathogenesis in these human populations. Further, this is in support of the basic and clinical researchers working on an interaction for a better understanding and medical care of mixed dementias, which have more complex factors than pure ones. However, to promote the translation of any therapeutical alternative is necessary to clarify the normative and the protocols for developing clinical trials with original candidates or work upon strategies proposed from South-American countries.

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The Animal Models of Dementia and Alzheimer’s Disease for Pre-Clinical Testing and Clinical Translation

Cited by 40 publications

References 0 publications

Hypertension drives parenchymal β‐amyloid accumulation in the brain parenchyma

Hypertension drives parenchymal β‐amyloid accumulation in the brain parenchyma

Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

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