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.

scholarly journals IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

2016 ◽  
Vol 113 (19) ◽  
pp. E2705-E2713 ◽  
Author(s):  
Amy K. Y. Fu ◽  
Kwok-Wang Hung ◽  
Michael Y. F. Yuen ◽  
Xiaopu Zhou ◽  
Deejay S. Y. Mak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Innate Immune Response ◽  
Memory Loss ◽  
Neuronal Loss ◽  
Innate Immune ◽  
Therapeutic Role ◽  
Potential Therapeutic Role ◽  
The Brain

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

Clinical and Magnetic Resonance Imaging Correlates of Hypothalamic–Pituitary–Adrenal Axis Function in Depression and Alzheimer's Disease

1996 ◽  
Vol 168 (6) ◽  
pp. 679-687 ◽  
Author(s):  
John T. O'Brien ◽  
David Ames ◽  
Isaac Schweitzer ◽  
Peter Colman ◽  
Patricia Desmond ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Magnetic Resonance ◽  
Hpa Axis ◽  
Hippocampal Atrophy ◽  
Resonance Imaging ◽  
Hypothalamic Pituitary Adrenal ◽  
Cortisol Levels

BackgroundAn age-related dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory.MethodTo investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM–III–R Major Depression.ResultsControlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI.ConclusionAn association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

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.

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.

The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Yunchun Li ◽  
Haoxing Wu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Memory Loss ◽  
Related Research ◽  
Central Nervous System Disorders ◽  
G Protein Coupled

Abstract:: Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attentions were paid to the pathophysiology and therapeutic potential of purinergic signaling in central nervous system disorders. Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD follows a series of failures in recent years, more researchers focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, summaries the potential agents as modulators for the receptors of purinergic signaling in AD related research and treatments. Thus, our paper provided an insight for purinergic signaling in the development of anti-AD therapies.

Many caregivers of persons with memory loss or Alzheimer's disease are unaware of the abilities of their persons with AD to recall their drugs and medical histories

Dementia ◽  
2018 ◽  
pp. 147130121882096
Author(s):  
Thomas A Ala ◽  
GaToya Simpson ◽  
Marshall T Holland ◽  
Vajeeha Tabassum ◽  
Maithili Deshpande ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Medical Histories ◽  
With Memory
Sign in / Sign up

Export Citation Format

Share Document