Tag Archives: Cognition

Researchers have shown how brain connections, or synapses, are lost early in Alzheimer’s disease and demonstrated that the process starts — and could potentially be halted — before telltale plaques accumulate in the brain. Their work, published online by Science, suggests new therapeutic targets to preserve cognitive function early in Alzheimer’s disease.

The researchers show in multiple Alzheimer’s mouse models that mechanisms similar to those used to “prune” excess synapses in the healthy developing brain are wrongly activated later in life. By blocking these mechanisms, they were able to reduce synapse loss in the mice.

Currently, there are five FDA-approved drugs for Alzheimer’s, but these only boost cognition temporarily and do not address the root causes of cognitive impairment in Alzheimer’s. Many newer drugs in the pipeline seek to eliminate amyloid plaque deposits or reduce inflammation in the brain, but the new research from Boston Children’s suggests that Alzheimer’s could be targeted much earlier, before these pathologic changes occur.

“Synapse loss is a strong correlate of cognitive decline,” says Beth Stevens, assistant professor in the Department of Neurology at Boston Children’s, senior investigator on the study and a recent recipient of the MacArthur “genius” grant. “We’re trying to go back to the very beginning and see how synapse loss starts.”

The researchers looked at Alzheimer’s — a disease of aging — through an unusual lens: normal brain development in infancy and childhood. Through years of research, the Stevens lab has shown that normal developing brains have a process to “prune” synapses that aren’t needed as they build their circuitry.

“Understanding a normal developmental process deeply has provided us with novel insight into how to protect synapses in Alzheimer’s and potentially a host of other diseases,” says Stevens, noting that synapse loss also occurs in frontotemporal dementia, Huntington’s disease, schizophrenia, glaucoma and other conditions.

In the Alzheimer’s mouse models, the team showed that synapse loss requires the activation of a protein called C1q, which “tags” synapses for elimination. Immune cells in the brain called microglia then “eat” the synapses — similar to what occurs during normal brain development. In the mice, C1q became more abundant around vulnerable synapses before amyloid plaque deposits could be observed.

When Stevens and colleagues blocked C1q, a downstream protein called C3, or the C3 receptor on microglia, synapse loss did not occur.

“Microglia and complement are already known to be involved in Alzheimer’s disease, but they have been largely regarded as a secondary event related to plaque-related neuroinflammation, a prominent feature in progressed stages of Alzheimer’s,” notes Soyon Hong, the Science paper’s first author. “Our study challenges this view and provides evidence that complement and microglia are involved much earlier in the disease process, when synapses are already vulnerable, and could potentially be targeted to preserve synaptic health.”

A human form of the antibody Stevens and Hong used to block C1q, known as ANX-005, is in early therapeutic development with Annexon Biosciences (San Francisco) and is being advanced into the clinic. The researchers believe it has potential to be used someday to protect against synapse loss in a variety of neurodegenerative diseases.

“One of the things this study highlights is the need to look for biomarkers for synapse loss and dysfunction,” says Hong. “As in cancer, if you treat people at a later stage of Alzheimer’s, it may already be too late.”

The researchers also found that the beta-amyloid protein, C1q and microglia work together to cause synapse loss in the early stages of Alzheimer’s. The oligomeric form of beta-amyloid (multiple units of beta-amyloid strung together) is already known to be toxic to synapses even before it forms plaque deposits, but the study showed that C1q is necessary for this effect. The converse was also true: microglia engulfed synapses only when oligomeric beta-amyloid was present.

Source: Reprinted from materials provided by Boston Children’s Hospital
Paper: “Complement and microglia mediate early synapse loss in Alzheimer mouse models”

The Joint Programming Initiative “A Healthy Diet for A Healthy Life” has launched a joint transnational call for research proposals in the area of Nutrition and Cognitive Function.

The joint action “Nutrition and Cognitive Function” (NutriCog) aims at promoting research activities that address the interrelation of diet and cognitive function. This knowledge will lay the basis for dietary preventive strategies and recommendations to guide individuals and populations towards health promoting dietary habits.

The objective of the NutriCog Call is to support ambitious, innovative and transnational collaborative research projects that will address important questions relating to the interplay between nutrition and cognitive function. Both the influence of dietary patterns (and/or dietary constituents, where appropriate) on cognitive functions and vice versa the effects of Central Nervous System nutrient signaling and cognitive processes on food intake, dietary patterns and eating behaviour are relevant for this call.

Proposals have to follow a multidisciplinary approach and should cover multiple areas, such as mechanistic/experimental research, translational research, epidemiological research and pilot/proof of principle studies for interventions.

Source: JPI-HDHL

The Joint Programming Initiative “A Healthy Diet for A Healthy Life” is launching a new joint transnational call for research proposals on “Nutrition and Cognitive Function”.

The call aims to support small transnational research consortia with innovative and interdisciplinary approaches tackling the interrelationships between nutrition and cognition.

The call is scheduled to be launched on March-30, 2015 with the deadline for proposal submission scheduled for June 8th, 2015.

The pre-call announcement is available here and through the link below:

 

Nutritional shortcomings are a key driver of age-related decline and disability whereas proper diet can increase years of healthy life. In support of the European Innovation Partnership on Active and Healthy Ageing, Joint Research Centre (JRC) scientists have reviewed the evidence on the role key nutrients and diet plays in promoting healthy ageing.

JRC scientists collected evidence on the prevention and treatment of age-related diseases with a focus on under-nutrition in older people, a main cause as well as a consequence of functional decline. The resulting report “The role of Nutrition in Active and Healthy Ageing” provides an important contribution to the overall target of the Partnership which is to increase the average healthy lifespan by two years by 2020, to enable EU citizens to lead healthy, active and independent lives while ageing and to improve the sustainability and efficiency of social and health care.