Genetics of Alzheimer’s Disease: Current Status and Future Development of Research

There is an urgent need to develop reliable and sensitive blood-based biomarkers of Alzheimer’s disease (AD) that can be used for screening and to increase the efficiency of clinical trials. The European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) discussed the current status of blood-based AD biomarker development at its 2018 annual meeting in Barcelona, Spain. Recent improvements in technologies to assess plasma levels of amyloid beta indicate that a single sample of blood could provide an accurate estimate of brain amyloid positivity. Plasma neurofilament light protein appears to provide a good marker of neurodegeneration, although not specific for AD. Plasma tau shows some promising results but weak or no correlation with CSF tau levels, which may reflect rapid clearance of tau in the bloodstream. Blood samples analyzed using -omics and other approaches are also in development and may provide important insight into disease mechanisms as well as biomarker profiles for disease prediction. To advance these technologies, international multidisciplinary, multi-stakeholder collaboration is essential.

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Repositioning of Immunomodulators: A Ray of Hope for Alzheimer’s Disease?

Frontiers in Neuroscience ◽

10.3389/fnins.2020.614643 ◽

2020 ◽

Vol 14 ◽

Author(s):

Antonio Munafò ◽

Chiara Burgaletto ◽

Giulia Di Benedetto ◽

Marco Di Mauro ◽

Rosaria Di Mauro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune System ◽

Neurodegenerative Disorder ◽

Drug Repositioning ◽

Amyloid Β ◽

Deep Understanding ◽

Current Status ◽

Age Related ◽

Tnf Α

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid β plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain’s pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.

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Learning from the Past: A Review of Clinical Trials Targeting Amyloid, Tau and Neuroinflammation in Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200304085513 ◽

2020 ◽

Vol 17 (2) ◽

pp. 112-125 ◽

Cited By ~ 5

Author(s):

Kelly Ceyzériat ◽

Thomas Zilli ◽

Philippe Millet ◽

Giovanni B. Frisoni ◽

Valentina Garibotto ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Animal Models ◽

Phase Iii ◽

Current Status ◽

Central Feature ◽

Phase Iii Trial ◽

The Past ◽

Positive Results

Alzheimer’s Disease (AD) is the most common neurodegenerative disease and cause of dementia. Characterized by amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau, AD pathology has been intensively studied during the last century. After a long series of failed trials of drugs targeting amyloid or Tau deposits, currently, hope lies in the positive results of one Phase III trial, highly debated, and on other ongoing trials. In parallel, some approaches target neuroinflammation, another central feature of AD. Therapeutic strategies are initially evaluated on animal models, in which the various drugs have shown effects on the target (decreasing amyloid, Tau and neuroinflammation) and sometimes on cognitive impairment. However, it is important to keep in mind that rodent models have a less complex brain than humans and that the pathology is generally not fully represented. Although they are indispensable tools in the drug discovery process, results obtained from animal models must be viewed with caution. In this review, we focus on the current status of disease-modifying therapies targeting amyloid, Tau and neuroinflammation with particular attention on the discrepancy between positive preclinical results on animal models and failures in clinical trials.

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Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease

Molecules ◽

10.3390/molecules24234255 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4255 ◽

Cited By ~ 6

Author(s):

Mohammad Afzal ◽

Amina Redha ◽

Redha AlHasan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Fruits And Vegetables ◽

Daily Intake ◽

Natural Antioxidants ◽

Current Status ◽

Ros Generation ◽

Amyloid Peptides ◽

Nitrogen Reactive Species ◽

Relationship Of

Anthocyanins (ANTs) are plant pigments that belong to a flavanol class of polyphenols and have diverse pharmacological properties. These compounds are primarily found in fruits and vegetables, with an average daily intake of 180 mgd−1 of these compounds in the developed world. ANTs are potent antioxidants that might regulate the free radical-mediated generation of amyloid peptides (Abeta-amyloids) in the brain, which causes Alzheimer’s disease (AD). This study presents a literature review of ANTs from different berries and their potential therapeutic value, with particular emphasis on neurodegenerative AD, which owing to oxidative stress. This review also highlights reactive oxygen species (ROS) generation through energy metabolism, nitrogen reactive species, the role of transition metals in generating ROS, and the radical-quenching mechanisms of natural antioxidants, including ANTs. The current status of the bioavailability, solubility, and structure activity relationship of ANTs is discussed herein.

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Influence of Woodsmoke Exposure on Molecular Mechanisms Underlying Alzheimer’s Disease: Existing Literature and Gaps in Our Understanding

Epigenetics Insights ◽

10.1177/2516865720954873 ◽

2020 ◽

Vol 13 ◽

pp. 251686572095487

Author(s):

Adam Schuller ◽

Luke Montrose

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Air Pollution ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

Ambient Air ◽

The United States ◽

Ambient Air Pollution ◽

Current Status

Woodsmoke poses a significant health risk as a growing component of ambient air pollution in the United States. While there is a long history of association between woodsmoke exposure and diseases of the respiratory, circulatory, and cardiovascular systems, recent evidence has linked woodsmoke exposure to cognitive dysfunction, including Alzheimer’s disease dementia. Alzheimer’s disease is a progressive neurodegenerative disorder with largely idiopathic origins and no known cure. Here, we explore the growing body of literature which relates woodsmoke-generated and ambient air pollution particulate matter exposure to Alzheimer’s disease (AD) onset or exacerbation, in the context of an inflammation-centric view of AD. Epigenetic modifications, specifically changes in DNA methylation patterns, are well documented following woodsmoke exposure and have been shown to influence disease-favoring inflammatory cascades, induce oxidative stress, and modulate the immune response in vitro, in vivo, and in humans following exposure to air pollution. Though the current status of the literature does not allow us to draw definitive conclusions linking these events, this review highlights the need for additional work to fill gaps in our understanding of the directionality, causality, and susceptibility throughout the life course.

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Current Status of the Neurobiology of Alzheimer's Disease and the Importance of Early Diagnosis

Journal of the International Neuropsychological Society ◽

10.1017/s1355617702214010 ◽

2002 ◽

Vol 8 (4) ◽

pp. 596-597

Author(s):

Edith V. Sullivan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Longitudinal Study ◽

Early Diagnosis ◽

Medical Treatment ◽

Accurate Diagnosis ◽

Current Status ◽

Age Related ◽

Loss Of Dignity ◽

Scientific Rationale

Alzheimer's disease—occurring upward of 15% of individuals age 65 and older—is the most prevalent age-related dementia. Since the late 1970s, neuropsychologists have been instrumental in identifying patterns of sparing and impairment of cognitive, sensory, and motor functions and rates of declines in selective functions. Anyone who has engaged in longitudinal study of AD and anyone of that large segment of the population with relatives suffering with AD has witnessed first-hand the relentless, irreversible demise of function and ultimate loss of dignity characteristic of AD's course. The approach of Scinto and Daffner's edited book, Early Diagnosis of Alzheimer's Disease, avoids rehashing the already established descriptions of AD and provides firm, scientific rationale for the meaningfulness of early and accurate diagnosis of AD despite its current dire prognosis and lack of effective medical treatment.

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