Advances in Alzheimer's Disease: Where Do We Stand in 2020?

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (15 March 2021) | Viewed by 27007

Special Issue Editor


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Guest Editor
Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri, USA
Interests: Alzheimer’s disease; Vascular dementia; Cerebral amyloid angiopathy

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD), a devastating chronic neurodegenerative disease, is the primary cause of dementia in the elderly. Neuropathologically, it is characterized by the deposition of amyloid plaques and formation of neurofibrillary tangles, leading to oxidative stress, neuroinflammation, neuronal loss and cholinergic dysfunction, and finally, the loss of various cognitive functions including learning and memory. Previous research has linked several lifestyle-related risk factors, such as diabetes, hypertension, small vessels disease, and cerebral stroke, to the exacerbation of AD. Therefore, by managing these risk factors, we can delay the disease’s progression. Currently, available therapy provides only symptomatic treatment. Thus, there is an urgent need to develop therapies including allopathic medicines, herbal medicines, or complementary treatments. Additionally, the development of biomarkers that allow the early detection of AD is needed.

This Special Issue of Brain Sciences is dedicated to expanding the knowledge of the complex pathology, diagnosis, and therapeutic interventions associated with Alzheimer’s disease. Furthermore, we aim to investigate the potential of new techniques such as optogenetics and chemogenetics for AD treatment as well as the use of exercise and cognitive training as AD preventive therapy. I invite authors and research groups to submit review articles, research articles, or commentaries related to recent advances in AD pathology, diagnosis, treatment options, and animal models.

Dr. Jogender Mehla
Guest Editor

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Keywords

  • Alzheimer’s disease
  • amyloid plaques
  • neurofibrillary tangles
  • cholinergic hypothesis
  • oxidative stress
  • neuroinflammation
  • herbal medicine
  • natural products

Published Papers (4 papers)

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Research

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16 pages, 4264 KiB  
Article
Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats
by Vandna Verma, Devendra Singh and Reeta KH
Brain Sci. 2020, 10(12), 923; https://doi.org/10.3390/brainsci10120923 - 30 Nov 2020
Cited by 35 | Viewed by 3373
Abstract
The role of oxidative stress, neuro-inflammation and cholinergic dysfunction is already established in the development of Alzheimer’s disease (AD). Sinapic acid (SA), a hydroxylcinnamic acid derivative, has shown neuro-protective effects. The current study evaluates the neuro-protective potential of SA in intracerebroventricular streptozotocin (ICV-STZ) [...] Read more.
The role of oxidative stress, neuro-inflammation and cholinergic dysfunction is already established in the development of Alzheimer’s disease (AD). Sinapic acid (SA), a hydroxylcinnamic acid derivative, has shown neuro-protective effects. The current study evaluates the neuro-protective potential of SA in intracerebroventricular streptozotocin (ICV-STZ) induced cognitive impairment in rats. Male Wistar rats were bilaterally injected with ICV-STZ. SA was administered intragastrically once daily for three weeks. Rats were divided into sham, ICV-STZ, STZ + SA (10 mg/kg), STZ + SA (20 mg/kg) and SA per se (20 mg/kg). Behavioral tests were assessed on day 0 and 21 days after STZ. Later, rats were sacrificed for biochemical parameters, pro-inflammatory cytokines, choline acetyltransferase (ChAT) expression and neuronal loss in the CA1 region of the hippocampus. The results showed that SA 20 mg/kg significantly (p < 0.05) improved cognitive impairment as assessed by Morris water maze and passive avoidance tests. SA 20 mg/kg reinstated the altered levels of GSH, MDA, TNF-α and IL-1β in the cortex and hippocampus. STZ-induced decreased expression of ChAT and neuronal loss were also significantly (p < 0.05) improved with SA. Our results showed that SA exhibits neuro-protection against ICV-STZ induced oxidative stress, neuro-inflammation, cholinergic dysfunction and neuronal loss, suggesting its potential in improving learning and memory in patients of AD. Full article
(This article belongs to the Special Issue Advances in Alzheimer's Disease: Where Do We Stand in 2020?)
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Review

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31 pages, 961 KiB  
Review
Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment
by Jogender Mehla, Pooja Gupta, Monika Pahuja, Deepti Diwan and Diksha Diksha
Brain Sci. 2020, 10(12), 964; https://doi.org/10.3390/brainsci10120964 - 10 Dec 2020
Cited by 42 | Viewed by 13197
Abstract
Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson’s disease and epilepsy, is a major health issue. The present review focuses on Alzheimer’s disease (AD), since it is the most important cause of cognitive impairment. It is characterized by [...] Read more.
Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson’s disease and epilepsy, is a major health issue. The present review focuses on Alzheimer’s disease (AD), since it is the most important cause of cognitive impairment. It is characterized by progressive memory loss, language deficits, depression, agitation, mood disturbances and psychosis. Although the hallmarks of AD are cholinergic dysfunction, β-amyloid plaques and neurofibrillary tangle formation, it is also associated with derangement of other neurotransmitters, elevated levels of advanced glycation end products, oxidative damage, neuroinflammation, genetic and environmental factors. On one hand, this complex etiopathology makes a response to commonly used drugs such as donepezil, rivastigmine, galantamine and memantine less predictable and often unsatisfactory. On the other hand, it supports the use of herbal medicines due to their nonspecific antioxidant and anti-inflammatory activity and specific cholinesterase inhibitory activity. The popularity of herbal medicines is also increasing due to their perceived effectiveness, safety and affordability. In the present article, the experimental and clinical evidence have been reviewed for various Indian herbal medicines such as Centella asiatica, Bacopa monnieri, Curcuma longa, Clitoria ternatea, Withania somnifera, Celastrus paniculatus, Evolvulus alsinoides, Desmodium gangeticum, Eclipta alba, Moringa oleifera and Convolvulus pluricaulis, which have shown potential in cognitive impairment. Some commonly available herbal formulations for memory impairment in India have also been reviewed. Full article
(This article belongs to the Special Issue Advances in Alzheimer's Disease: Where Do We Stand in 2020?)
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33 pages, 2090 KiB  
Review
Dysregulated Wnt Signalling in the Alzheimer’s Brain
by Nozie D. Aghaizu, Hanqing Jin and Paul J. Whiting
Brain Sci. 2020, 10(12), 902; https://doi.org/10.3390/brainsci10120902 - 24 Nov 2020
Cited by 27 | Viewed by 7027
Abstract
The Wnt signalling system is essential for both the developing and adult central nervous system. It regulates numerous cellular functions ranging from neurogenesis to blood brain barrier biology. Dysregulated Wnt signalling can thus have significant consequences for normal brain function, which is becoming [...] Read more.
The Wnt signalling system is essential for both the developing and adult central nervous system. It regulates numerous cellular functions ranging from neurogenesis to blood brain barrier biology. Dysregulated Wnt signalling can thus have significant consequences for normal brain function, which is becoming increasingly clear in Alzheimer’s disease (AD), an age-related neurodegenerative disorder that is the most prevalent form of dementia. AD exhibits a range of pathophysiological manifestations including aberrant amyloid precursor protein processing, tau pathology, synapse loss, neuroinflammation and blood brain barrier breakdown, which have been associated to a greater or lesser degree with abnormal Wnt signalling. Here we provide a comprehensive overview of the role of Wnt signalling in the CNS, and the research that implicates dysregulated Wnt signalling in the ageing brain and in AD pathogenesis. We also discuss the opportunities for therapeutic intervention in AD via modulation of the Wnt signalling pathway, and highlight some of the challenges and the gaps in our current understanding that need to be met to enable that goal. Full article
(This article belongs to the Special Issue Advances in Alzheimer's Disease: Where Do We Stand in 2020?)
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16 pages, 345 KiB  
Review
Contributions of Molecular and Optical Techniques to the Clinical Diagnosis of Alzheimer’s Disease
by Edoardo Bistaffa, Fabrizio Tagliavini, Paolo Matteini and Fabio Moda
Brain Sci. 2020, 10(11), 815; https://doi.org/10.3390/brainsci10110815 - 3 Nov 2020
Cited by 9 | Viewed by 2571
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. The distinctive neuropathological feature of AD is the intracerebral accumulation of two abnormally folded proteins: β-amyloid (Aβ) in the form of extracellular plaques, and tau in the form of intracellular neurofibrillary tangles. These [...] Read more.
Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. The distinctive neuropathological feature of AD is the intracerebral accumulation of two abnormally folded proteins: β-amyloid (Aβ) in the form of extracellular plaques, and tau in the form of intracellular neurofibrillary tangles. These proteins are considered disease-specific biomarkers, and the definite diagnosis of AD relies on their post-mortem identification in the brain. The clinical diagnosis of AD is challenging, especially in the early stages. The disease is highly heterogeneous in terms of clinical presentation and neuropathological features. This phenotypic variability seems to be partially due to the presence of distinct Aβ conformers, referred to as strains. With the development of an innovative technique named Real-Time Quaking-Induced Conversion (RT-QuIC), traces of Aβ strains were found in the cerebrospinal fluid of AD patients. Emerging evidence suggests that different conformers may transmit their strain signature to the RT-QuIC reaction products. In this review, we describe the current challenges for the clinical diagnosis of AD and describe how the RT-QuIC products could be analyzed by a surface-enhanced Raman spectroscopy (SERS)-based systems to reveal the presence of strain signatures, eventually leading to early diagnosis of AD with the recognition of individual disease phenotype. Full article
(This article belongs to the Special Issue Advances in Alzheimer's Disease: Where Do We Stand in 2020?)
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