Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics.

The so-called "amyloid cascade hypothesis" provides an elegant explanation of Alzheimer's disease (AD), has motivated the amyloid-lowering therapeutic strategy, and led to the elaboration of a rich experimental and conceptual toolkit for the field to progress. But it might be incorrect. The scientific evidence base supporting the efficacy and safety of current anti-amyloid antibody treatments in AD is weak.

Survival time in Alzheimer's disease: An overlooked measure of safety and efficacy of disease-modifying therapies.

It is of vital importance to patients and physicians, as well as administrators and drug regulators, that the treatment for a disease has been shown to be safe and clinically meaningful in long-term use. Recent literature has highlighted 3 major categories of arguments for and against modification of the underlying disease process in Alzheimer's disease (AD): pathophysiology, biomarkers and data from clinical trials. We argue that the Alzheimer's arena is over-reliant on theories of disease modification based solely on brain positron emission tomography (PET) imaging and blood biomarkers of tau and Aβ peptides.

The Amyloid Cascade Hypothesis in Alzheimer's Disease: Should We Change Our Thinking?

Old age increases the risk of Alzheimer's disease (AD), the most common neurodegenerative disease, a devastating disorder of the human mind and the leading cause of dementia. Worldwide, 50 million people have the disease, and it is estimated that there will be 150 million by 2050. Today, healthcare for AD patients consumes 1% of the global economy.

Alzheimer's trials: A cul-de-sac with no end in sight.

We don’t understand Alzheimer, its origin and disease mechanisms. The absence of disease-modifying treatments for Alzheimer today is due to the amyloid hypothesis, a misguided hypothesis of Alzheimer’s disease etiology, which has dominated Alzheimer research, drug development, and clinical trials for 30 years. However, the hypothesis is not dead yet, as exemplified by the recent resurrection of clinical trials with aducanumab.

Ovarian cancer evolution through stochastic genome alterations: defining the genomic role in ovarian cancer.

Ovarian cancer is the fifth leading cause of death among women worldwide. Characterized by complex etiology and multi-level heterogeneity, its origins are not well understood. Intense research efforts over the last decade have furthered our knowledge by identifying multiple risk factors that are associated with the disease.

Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer.

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis.