Resolving controversies on the path to Alzheimer's therapeutics

More than a century ago Alois Alzheimer published a case study that later evolved into the Amyloid Cascade hypothesis—which assumes that increasing proliferation of plaques and tangles in the brain cause dementia. However, studies involving the removal of plaques—amyloid-β—in patients' brains resulted in worse cognitive performance, suggesting that plaques cannot solely be the disease. The search then focused on tau misfolded protein. But the evidence is uncertain. This paper suggests a critical history approach to understanding this confusion in Alzheimer's disease research. Confusion is related to variability in expression of the disease, inaccuracy of clinical diagnostic tools, the relationship to other diseases, and the increasing neurological variance among older adults. The final verdict is that there is an unclear relationship between the biology and the expression of the disease. Alzheimer's disease may in fact be the expression of another, yet unknown, disease. An often overlooked component in Alzheimer's disease is white matter in the brain. Although found to be negatively related to dementia and positively related to learning, white matter remains unexamined in most current research. Historical evidence suggests that this was not the case a century ago. This paper is grounded in historical observations that Alois Alzheimer and his contemporaries identified these criticisms a hundred years ago. By ignoring these criticisms today, we have ended in a research cul de sac. This paper argues for greater specificity of the definition of Alzheimer's disease and a broadening of the research focus to include the possible role of epigenetic changes, variance within older ages and brain plasticity. Only by broadening the scope of research and addressing this confusion directly can we move out of this research cul de sac and move closer to a cure.

Journal of Alzheimer's disease : JAD, 2015

Scientific reports hold a mirror up to a culture, reflecting the beliefs, values, assumptions, practices, technologies, and political-economic interests that shape discourse around particular diseases in particular cultural moments [1]. Indeed, despite their authoritative patina, such reports are "living documents" that invite critical analysis about where discourse in a particular field has been and where it is going. In this spirit, two recent reports from the Alzheimer's Association (Changing the Trajectory of Alzheimer's Disease: How a Treatment by 2025 Saves Lives and Dollars) and the Institute of Medicine in the United States (Cognitive Aging: Progress in Understanding and Opportunities for Action) are worthy of attention from those endeavoring to understand and contextualize the science and politics of brain health, aging, and dementia [2].

2013

A lzheimer's disease (AD) is a progressive neurodegenerative disorder that devastates the brain-affecting cognitive function, memory, visual spatial perception, abstract thinking, and eventually loss of bodily functions. Based on the latest Rand report on dementia and AD, the current costs in lives lost, families shattered, careers disrupted, and financial futures ruined is much too high. And with the projected increases in the number of individuals affected by AD and related dementias in coming years, the global costs become unendurable and insupportable. Many pharmaceutical companies have dismantled their AD treatment discovery programs because of failed experimental therapeutics in costly Phase III clinical trials. Recently, a paradigm shift to focus earlier in the disease process to include preclinical populations with mild cognitive impairment (MCI) due to AD has emerged. 1-3 It is antici

Journal of Alzheimer's Disease, 2022

The Lancet Neurology, 2003

Frontiers in pharmacology, 2014

Alzheimer's Disease (AD) is the most common form of dementia, affecting approximately 36 million people worldwide. To date there is no preventive or curative treatment available for AD, and in absence of major progress in therapeutic development, AD manifests a concrete socioeconomic threat. The awareness of the growing problem of AD is increasing, exemplified by the recent G8 Dementia Summit, a meeting held in order to set the stage and steer the compass for the future. Simultaneously, and paradoxically, we have seen key players in the pharmaceutical industry that have recently closed or significantly decreased their R&D spending on AD and other CNS disorders. Given the pressing need for new treatments in this area, other actors need to step-in and enter this drug discovery arena complementing the industrial efforts, in order to turn biological and technological progress into novel therapeutics. In this article, we present an example of a novel drug discovery initiative that in...

European Journal of Nuclear Medicine and Molecular Imaging

drug against Alzheimer's disease (AD), aducanumab (Aduhelm™), has been approved in the USA by the Food and Drug Administration (FDA). This event already has had a major impact, as shown by the storm of commentaries, both in favor and against it, in journals and social media before and after its disclosure. Its impact is linked to a number of factors: AD is a devastating and incurable disease with a dramatic toll on both patients and their families; Aducanumab is the first approved drug that was tested for its ability to influence the course of the disease (disease-modifying drug) and not only to treat This article is part of the Topical Collection on Neurology

انواع تغطية االسقف والسطح - د جميضة - types shingles roof, 2024

انواع واشكال تغطية بلاطات الأسقف والأسطحة والعزل المائي والحراري اضغط على الصورة او العنوان تحصل على الفايل