Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 10.04.2019
Verubecestat Failed to Slow Progression of Early Alzheimer’s Disease
MedicalResearch.com Interview with:
Michael F. Egan, MD
Vice President, Neuroscience
Global Clinical Development
Merck Research Laboratories
North Wales, PA
MedicalResearch.com: What is the background for this study?
Response: Alzheimer’s disease (AD) appears to be due to the gradual accumulation of amyloid over many years (the “amyloid hypothesis”). At some point, it is thought that amyloid triggers abnormalities in tau, which then forms deposits within neurons and leads to progressive neurodegeneration.
Amyloid is made up of a small, sticky peptide, Abeta, which is produced when the enzyme BACE cleaves a large protein called APP. In our trial, we tested whether a potent BACE inhibitor, verubecestat, could slow disease progression in subjects with early AD (or prodromal AD) by blocking formation of Abeta. A previous trial in subjects with dementia due to AD failed to find evidence of efficacy.
One possible reason for this failure is that subjects had too much amyloid in their brain already.
Michael F. Egan, MD
Vice President, Neuroscience
Global Clinical Development
Merck Research Laboratories
North Wales, PA
MedicalResearch.com: What is the background for this study?
Response: Alzheimer’s disease (AD) appears to be due to the gradual accumulation of amyloid over many years (the “amyloid hypothesis”). At some point, it is thought that amyloid triggers abnormalities in tau, which then forms deposits within neurons and leads to progressive neurodegeneration.
Amyloid is made up of a small, sticky peptide, Abeta, which is produced when the enzyme BACE cleaves a large protein called APP. In our trial, we tested whether a potent BACE inhibitor, verubecestat, could slow disease progression in subjects with early AD (or prodromal AD) by blocking formation of Abeta. A previous trial in subjects with dementia due to AD failed to find evidence of efficacy.
One possible reason for this failure is that subjects had too much amyloid in their brain already.



Dr. Zhong[/caption]
Victor Wenze Zhong, Ph.D.
Postdoctoral fellow
Department of Preventive Medicine
Feinberg School of Medicine
Northwestern University
Chicago, IL 60611
MedicalResearch.com: What is the background for this study?
Response: Dietary cholesterol is a common nutrient in human diet. Eggs, specially egg yolks, are the single richest source of dietary cholesterol among all commonly consumed foods. The associations between dietary cholesterol consumption and cardiovascular disease and mortality remain controversial despite decades of research. Eating less than 300 mg of dietary cholesterol per day was the guideline recommendation before 2015. However, the most recent 2015-2020 Dietary Guidelines for Americans no longer include a daily consumption limit for dietary cholesterol and recommend weekly egg consumption as part of the healthy US-style eating pattern. Whether these recommendations are appropriate have been intensely debated.

Joanne B. Newbury, PhD
ESRC Postdoctoral Fellow
King’s College London
Social, Genetic & Developmental Psychiatry Centre
Institute of Psychiatry, Psychology & Neuroscience
London, United Kingdom
MedicalResearch.com: What is the background for this study?
Response: Urban living is one of the most well-established risk factors for adult psychotic disorders such as schizophrenia. However, less is known about the role of the urban environment in subclinical psychotic experiences in childhood and adolescence, such as hearing voices and extreme paranoia. These early psychotic experiences are a developmental risk factor for adult psychotic disorders and a range of other serious mental health problems such as depression and anxiety.
It is therefore important that we understand what factors might contribute to the development of early psychotic experiences so that we might be able to intervene and prevent their onset and progression.
In a cohort of over 2000 UK-born children (The Environmental Risk Longitudinal Twin Study), we have previously shown that subclinical psychotic experiences are also around twice as common among children and teenagers raised in urban versus rural settings. We have also shown that this appears to be partly explained by social features in urban neighbourhoods such as higher crime levels and lower levels of social cohesion.
However, no studies have examined the potential link between air pollution and psychotic experiences. This is despite air pollution being a major health problem worldwide (particularly in cities), and despite emerging evidence linking air pollution to the brain.