P4-005: SELF-REPORTED APOE GENOTYPE IN THE BRAIN HEALTH REGISTRY: ASSOCIATIONS WITH MEMORY AND ASSESSMENT OF APOE 4+ PARTICIPANTS ELIGIBLE FOR ALZHEIMER'S DISEASE CLINICAL TRIALS

Alzheimer’s disease is one form of dementia affecting a significant proportion of the population. The etiology of this prevalent disease is currently unknown. It is postulated that AD can be treated by using stem cell-based therapies by replacing the lost neurons in the atrophic regions of the brain. For these novel therapies to be successful several sources of stem cells have been proposed, such as pluripotent stem cells as well as multipotent stem cells. Proof of concept in animal studies have shown that stem cells can grafted into the affected regions or delivered intravenously into affected parts of the brain. These experiments had improved cognition and memory performance in rodents. The promising results seen in animal models have increased interest in conducting clinical trials using the same technique. In the last 5 years, several treatments have reached phase II clinical trials.

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Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease

International Journal of Alzheimer s Disease ◽

10.1155/2012/868972 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Izumi Maezawa ◽

David Paul Jenkins ◽

Benjamin E. Jin ◽

Heike Wulff

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Brain Injuries ◽

Potential Therapeutic Target ◽

Neuroprotective Effects ◽

Anti Inflammatory ◽

Calcium Activated Potassium Channel ◽

The Brain ◽

Phagocytosis Activity

There exists an urgent need for new target discovery to treat Alzheimer’s disease (AD); however, recent clinical trials based on anti-Aβand anti-inflammatory strategies have yielded disappointing results. To expedite new drug discovery, we propose reposition targets which have been previously pursued by both industry and academia for indications other than AD. One such target is the calcium-activated potassium channel KCa3.1 (KCNN4), which in the brain is primarily expressed in microglia and is significantly upregulated when microglia are activated. We here review the existing evidence supporting that KCa3.1 inhibition could block microglial neurotoxicity without affecting their neuroprotective phagocytosis activity and without being broadly immunosuppressive. The anti-inflammatory and neuroprotective effects of KCa3.1 blockade would be suitable for treating AD as well as cerebrovascular and traumatic brain injuries, two well-known risk factors contributing to the dementia in AD patients presenting with mixed pathologies. Importantly, the pharmacokinetics and pharmacodynamics of several KCa3.1 blockers are well known, and a KCa3.1 blocker has been proven safe in clinical trials. It is therefore promising to reposition old or new KCa3.1 blockers for AD preclinical and clinical trials.

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Konsumsi Kopi untuk Mencegah Penyakit Alzheimer

Jurnal Ilmiah Kesehatan Sandi Husada ◽

10.35816/jiskh.v12i2.439 ◽

2020 ◽

Vol 12 (2) ◽

pp. 996-1002

Author(s):

Bimo Husodo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Skills ◽

Coffee Consumption ◽

Brain Health ◽

Literature Study ◽

National Journal ◽

Positive Effects ◽

The Brain ◽

Preventive Effects

Abstract. Coffee is one of the most consumed beverages in the world and most adults drink coffee every day. Coffee contains hundreds of bioactive compounds, including caffeine, chlorogenic acid, polyphenols, and small amounts of minerals and vitamins, which are known to have positive effects on brain health. Alzheimer's disease is a degenerative disease of the brain and the most common cause of dementia characterized by decreased memory, language, problem solving and other cognitive skills that affect a person's ability to perform daily activities. The purpose of this literature study is to determine the benefits of coffee consumption in preventing Alzheimer's disease. Method. This research is a literature study and library sources used involving 15 libraries from 1 national journal and 14 international journals. Result. Several studies have shown the preventive effects of coffee on Alzheimer's disease and cognitive decline through various mechanisms such as a role in lowering plasma Aβ levels, as well as an antioxidant that can reduce inflammation and protect against dementia. Conclusion. Coffee can have a protective effect on Alzheimer's disease and is safe to consume if it does not exceed the recommended dosage. Abstract. Kopi adalah salah satu minuman yang paling banyak dikonsumsi di dunia dan sebagian besar or ang dewasa minum kopi setiap hari. Kopi mengandung ratusan senyawa bioaktif, termasuk kafein, asam klorogenat, polifenol, dan sejumlah kecil mineral dan vitamin yang di antaranya diketahui memiliki efek positif bagi kesehatan otak. Penyakit Alzheimer adalah penyakit degeneratif pada otak dan penyebab paling umum dari demensia yang ditandai dengan penurunan daya ingat, bahasa, pemecahan masalah, dan keterampilan kognitif lain yang memengaruhi kemampuan seseorang untuk melakukan aktivitas sehari-hari. Tujuan dari studi literatur ini adalah untuk mengetahui manfaat konsumsi kopi untuk mencegah penyakit Alzheimer. Metode. Penelitian ini merupakan studi literatur dan sumber pustaka yang digunakan melibatkan 15 pustaka yang berasal dari 1 jurnal nasional dan 14 jurnal internasional. Hasil. Beberapa studi menunjukkan efek pencegahan dari kopi pada penyakit Alzheimer dan penurunan kognitif melalui berbagai mekanisme misalnya berperan dalam penurunan kadar Aβ plasma,serta sebagai antioksidan yang dapat mengurangi peradangan dan melindungi dari demensia. Kesimpulan. Kopi dapat memberikan efek protektif pada penyakit alzheimer serta aman dikonsumsi apabila tidak melebihi dosis yang dianjurkan

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Fluid Biomarkers in Clinical Trials for Alzheimer’s Disease: Current and Future Application

Journal of Alzheimer s Disease ◽

10.3233/jad-201068 ◽

2021 ◽

pp. 1-14

Author(s):

Jianwei Yang ◽

Longfei Jia ◽

Yan Li ◽

Qiongqiong Qiu ◽

Meina Quan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Future Application ◽

Comprehensive Overview ◽

Ongoing Research ◽

Drug Candidates ◽

The Many ◽

Almost All ◽

The Brain

Alzheimer’s disease (AD) research is entering a unique moment in which enormous information about the molecular basis of this disease is being translated into therapeutics. However, almost all drug candidates have failed in clinical trials over the past 30 years. These many trial failures have highlighted a need for the incorporation of biomarkers in clinical trials to help improve the trial design. Fluid biomarkers measured in cerebrospinal fluid and circulating blood, which can reflect the pathophysiological process in the brain, are becoming increasingly important in AD clinical trials. In this review, we first succinctly outline a panel of fluid biomarkers for neuropathological changes in AD. Then, we provide a comprehensive overview of current and future application of fluid biomarkers in clinical trials for AD. We also summarize the many challenges that have been encountered in efforts to integrate fluid biomarkers in clinical trials, and the barriers that have begun to be overcome. Ongoing research efforts in the field of fluid biomarkers will be critical to make significant progress in ultimately unveiling disease-modifying therapies in AD.

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Increase your Brainability—and Reduce your Risk of Dementia

10.1093/oso/9780198860341.001.0001 ◽

2021 ◽

Author(s):

Charles Alessi ◽

Larry W. Chambers ◽

Muir Gray

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Health Service ◽

Brain Tissue ◽

Blood Supply ◽

Medical Profession ◽

Brain Health ◽

The Mind ◽

The Brain

Our experience is that many people including many members of the medical profession are confused about what happens to our brains and minds as we live longer. Consistently, they overestimate the effects of ageing and underestimate the potential for improving the ability of the brain and the mind no matter what age you may be. Linked to this is the fact that, although Alzheimer’s disease cannot be prevented, the risk of dementia can be reduced by at least a third because there are many other causes of dementia than Alzheimer’s disease having to do with healthy brain tissue, blood supply to the brain and ability to interact with people and ideas. With this knowledge, we outline steps individuals can take themselves, with family and friends, their community and the health service to improve brain health.

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Cerebrovascular phenotypes in mouse models of Alzheimer’s disease

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21992462 ◽

2021 ◽

pp. 0271678X2199246

Author(s):

Jenny I Szu ◽

André Obenaus

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Models ◽

Time Course ◽

Morphological Changes ◽

The Elderly ◽

Functional Deficits ◽

Degenerative Disorder ◽

The Brain ◽

With Memory

Alzheimer’s disease (AD) is a devastating neurological degenerative disorder and is the most common cause of dementia in the elderly. Clinically, AD manifests with memory and cognitive decline associated with deposition of hallmark amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although the mechanisms underlying AD remains unclear, two hypotheses have been proposed. The established amyloid hypothesis states that Aβ accumulation is the basis of AD and leads to formation of NFTs. In contrast, the two-hit vascular hypothesis suggests that early vascular damage leads to increased accumulation of Aβ deposits in the brain. Multiple studies have reported significant morphological changes of the cerebrovasculature which can result in severe functional deficits. In this review, we delve into known structural and functional vascular alterations in various mouse models of AD and the cellular and molecular constituents that influence these changes to further disease progression. Many studies shed light on the direct impact of Aβ on the cerebrovasculature and how it is disrupted during the progression of AD. However, more research directed towards an improved understanding of how the cerebrovasculature is modified over the time course of AD is needed prior to developing future interventional strategies.

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