by Science Alert:

An Australian study has shown that plaque, long considered to be the hallmark of Alzheimer’s disease, is one of the last events to occur in the Alzheimer’s brain. This finding will impact the current debate about how best to diagnose and treat Alzheimer’s disease.

PhD student Amanda Wright and Dr Bryce Vissel from Sydney’s Garvan Institute of Medical Research studied a mouse model of Alzheimer’s disease in order to identify early versus late disease mechanisms and markers.

The data, published online today in the journal PLOS ONE, suggest that plaques occur long after memory loss, so may not be a useful early pathological marker for Alzheimer’s disease. The Investigators found that significant nerve cell loss and a range of brain pathologies, including inflammation, began at the same time as subtle memory problems appeared, early in the disease process. Plaques occurred much later, well after significant memory loss.  

by Jason Gate for Bloomberg:

Abnormal deposits in the brain thought to trigger Alzheimer’s disease can be detected decades before the memory-robbing illness ensues, a finding that will help guide future treatments, researchers in Australia said.

Doctors at Melbourne’s Austin Hospital followed 200 seniors, including people with Alzheimer’s disease and mild cognitive impairment, for more than three years to chart any decline in cognition and brain size against the deposition of abnormal protein in their brains. They found it takes about 20 years for the deposits, known as amyloid beta, to lead to dementia.

by Marjorie Montemayor-Quellenberg for Harvard Gazette:

Previous studies have shown that keeping the mind active, exercising, and social interactions may help delay the onset of dementia in Alzheimer’s patients.

Now, a new study led by Dennis Selkoe, co-director of the Center for Neurologic Diseases in the Department of Neurology at Brigham and Women’s Hospital (BWH), provides specific, pre-clinical scientific evidence supporting the concept that prolonged and intensive stimulation by an enriched environment — especially regular exposure to new activities — may have beneficial effects in delaying one of the key negative factors in Alzheimer’s disease.

Researchers at the Harvard-affiliated BWH used a wild-type mouse model when evaluating how the environment might affect Alzheimer’s. Unlike other pre-clinical models used in Alzheimer’s disease research, wild-type mice tend to more closely mimic the scenario of average humans developing the disease under normal environmental conditions, rather than being strongly genetically pre-disposed to the disease.

by Science Daily:

A study combining genetic data with brain imaging, designed to identify genes associated with the amyloid plaque deposits found in Alzheimer’s disease patients, has not only identified the APOE gene — long associated with development of Alzheimer’s — but has uncovered an association with a second gene, called BCHE.

A national research team, led by scientists at the Indiana University School of Medicine, reported the results of the study in an article inMolecular Psychiatry posted online February 19. The study is believed to be the first genome-wide association study of plaque deposits using a specialized PET scan tracer that binds to amyloid.

The research also is believed to be the first to implicate variations in the BCHE gene in plaque deposits visualized in living individuals who have been diagnosed with Alzheimer’s disease or are at-risk for developing the disease. The enzyme coded by the BCHE gene has previously been studied in post-mortem brain tissue and is known to be found in plaques.

by Science Codex:

Researchers at Washington University School of Medicine in St. Louis have found a key difference in the brains of people with Alzheimer’s disease and those who are cognitively normal but still have brain plaques that characterize this type of dementia.

“There is a very interesting group of people whose thinking and memory are normal, even late in life, yet their brains are full of amyloid beta plaques that appear to be identical to what’s seen in Alzheimer’s disease,” says David L. Brody, MD, PhD, associate professor of neurology. “How this can occur is a tantalizing clinical question. It makes it clear that we don’t understand exactly what causes dementia.”

Hard plaques made of a protein called amyloid beta are always present in the brain of a person diagnosed with Alzheimer’s disease, according to Brody. But the simple presence of plaques does not always result in impaired thinking and memory. In other words, the plaques are necessary – but not sufficient – to cause Alzheimer’s dementia.

by Kanoko Matsuyama for Businessweek:

People with plaques in the brain associated with Alzheimer’s disease may have a greater risk for cognitive impairment than those who have a gene tied to the dementia-causing illness, Australian researchers found.

In a study of 141 healthy subjects, those with clumps of amyloid beta plaques in their brains at the start of the study had as much as a 20 percent greater decline in memory and thinking over an 18-month period than those with fewer plaques. The research also showed that patients with the gene linked to Alzheimer’s, called ApoE4, had a greater mental decline, though having the gene didn’t alter the decline related to the plaques.

by Science Daily:

Swiss researchers have succeeded in generating detailed three-dimensional images of the spatial distribution of amyloid plaques in the brains of mice afflicted with Alzheimer’s disease. These plaques are accumulations of small pieces of protein in the brain and are a typical characteristic of Alzheimer’s.

The new technique used in the investigations provides an extremely precise research tool for a better understanding of the disease. In the future, scientists hope that it will also provide the basis for a new and reliable diagnosis method.

The results were achieved within a joint project of two teams of researchers — one from the Paul Scherrer Institute (PSI) and ETH Zurich, the other from the École Polytechnique Fédérale de Lausanne (EPFL). They have been published in the journal Neuroimage.

by Health News Digest:

The time may have come to scrub the idea that brain plaque — deposits of protein that clog passages between brain cells — might not be all that bad.

University of Florida researchers have discovered that people with no signs of dementia during their lives, even though their brains contained the debris typical of Alzheimer’s disease, probably would have experienced health problems had they lived longer, according to a study to appear this week in the open access journal Alzheimer’s Research & Therapy.

Scientists suspect patients who experience relatively few cognitive problems even with a substance called amyloid beta protein accumulating in their brains — the hallmark of Alzheimer’s disease — might collect a less toxic form of the so-called brain plaque.

But UF College of Medicine scientists with colleagues from the Mayo Clinic in Jacksonville found few differences when they compared the postmortem brain tissue of Alzheimer’s patients with that from people who accumulated plaque without symptoms, a condition known as pathological aging.

by UC San Diego Health System

Without p-tau protein present, impact of amyloid is “not significantly different from zero”

According to a new study, the neuron-killing pathology of Alzheimer’s disease (AD), which begins before clinical symptoms appear, requires the presence of both amyloid-beta (a-beta) plaque deposits and elevated levels of an altered protein called p-tau.

Without both, progressive clinical decline associated with AD in cognitively healthy older individuals is “not significantly different from zero,” reports a team of scientists at the University of California, San Diego School of Medicine in the April 23 online issue of theArchives of Neurology.

“I think this is the biggest contribution of our work,” said Rahul S. Desikan, MD, PhD, research fellow and resident radiologist in the UC San Diego Department of Radiology and first author of the study.  “A number of planned clinical trials – and the majority of Alzheimer’s studies – focus predominantly on a-beta. Our results highlight the importance of also looking at p-tau, particularly in trials investigating therapies to remove a-beta. Older, non-demented individuals who have elevated a-beta levels, but normal p-tau levels, may not progress to Alzheimer’s, while older individuals with elevated levels of both will likely develop the disease.”

by Washington University School of Medicine

Scientist studying the way Alzheimer’s takes root in the brain have identified important new similarities between a mouse model and human Alzheimer’s.

Researchers at Washington University School of Medicine in St. Louis have shown that brain plaques in mice are associated with disruption of the ability of brain regions to network with each other. This decline parallels earlier results from human studies, suggesting that what scientists learn about Alzheimer’s effects on brain networks in the mice will likely be transferable to human disease research.

The study, published in the Journal of Neuroscience, is among the first to precisely quantify the effects of Alzheimer’s disease plaques on brain networks in an animal model. Until now, scientists studying Alzheimer’s in animals have generally been limited to assessments of structural brain damage and analyses of brain cell activity levels.

“Precise measurement of changes in brain networks are critical to understanding Alzheimer’s and will likely be important in models of other neurodegenerative disorders,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “For example, we can now test whether blocking Alzheimer’s plaques from building up in the mouse brain prevents disruptions in brain networks.”