One of the key findings in Alzheimer’s disease is a loss of synaptic connections.
The synapse is the place where brain cells communicate with each other via their dendritic branches. The cells do not actually touch but are separated by a space called the synaptic cleft. It is across this space that brain chemicals or neurotransmitters cross to stimulate the adjoining brain cells and trigger further electrical messages to be passed along forming neural circuits or pathways.

Without synapses brain cells are unable to communicate to each other.

Sorry, I’m going to get a bit technical here, but it’s important to help understand the article.
Sets of particular proteins that bind together to form a molecular hub called the postsynaptic density or PSD occur at the synapse, in the terminals of the dendrites. Animal studies had previously shown that the PSD plays an important role in brain disease and behaviour. However until now, little has been known about the human PSD.

Researchers from the Welcome Trust Sanger Institute and Edinburgh University have used a technique called proteomics to extract PSD’s from the synapses of patients undergoing brain surgery. Their findings are quite remarkable.

They have discovered a total of 1461 proteins, each encoded by a different gene in these human synapses.
This then allowed them to systematically identify those diseases that affect the human synapse.

Professor Grant who led the research team revealed that over 130 brain diseases involve the PSD including Alzheimer’s, Parkinson’s, some forms of autism and learning disability.

Professor Noebels, Professor of Neurology, Neuroscience and Human Genetics at Baylor College of medicine said that of the 1461 proteins identified, “every seventh protein is involved in a known clinical disorder and half of them are repeat offenders. Researchers will now have a strategic starting point to start to unravel the complexity of brain disorders”

The research group has also created a first molecular network to show just how many of the proteins and diseases are interconnected.

As a sign of tremendous collaboration and desire to accelerate further discovery and use of this data, the scientists have released all of their findings into a public domain at their website G2Cdb
No wikileaks required here. It’s all there to be shared.

They suggest that the proteome of the PSD will help us to gain further understanding of the brain in the same way that the genome assisted our understanding of DNA.

Other fascinating findings Include:

• That the proteins in PSD are important for certain cognitive behaviours such as learning, memory, emotion and mood

• And also for social behaviours, addiction and drug abuse.

Looking at how the PSD has evolved over time and contrary to expectations, the researchers discovered that the PSD has been resistant to change over the millennia.
This means that synapses of rodents are not that dissimilar from humans, making further research using rat and mice models very suitable for studying human brain disease. Looks like we have more in common with our rodent friends than previously recognised.

These findings provide further valuable clues adding to our understanding of the brain and how some brain diseases may develop.

Àlex Bayés, Louie N van de Lagemaat, Mark O Collins, Mike D R Croning, Ian R Whittle, Jyoti S Choudhary, Seth G N Grant. Characterisation of the proteome, diseases and evolution of the human postsynaptic density. Nature Neuroscience, December 19, 2010 DOI: 10.1038/nn.2719

Diabetes is a recognised risk factor for dementia.
It is also associated with a higher risk of depression and eating disorders.
What has now been found is that diabetes affects how much cholesterol our brain can make.

That’s right, our brain makes it’s own cholesterol that it uses to form synapses (the connections between brain cells). It is also used to form the vesicles or storage structures located at the synapse that contain the neurotransmitters, the brain’s chemicals that are passed from one brain cell to the next. We have a “fat” head and it is essential the brain can produce sufficient cholesterol for healthy brain function. Having too little cholesterol in the brain is associated with Alzheimer’s disease and other neurodegenerative conditions.

Studies using mice with type 1 (insulin deficient) diabetes looked at gene expression in an area of the brain called the hypothalamus. It was found that in these mice, gene expression for the synthesis of cholesterol was reduced. Treating them using insulin reversed the problem.
They also found that those mice with unable to synthesise brain cholesterol gained more weight and ate more, indicating that diabetes may affect those brain hormones associated with appetite regulation.

This finding adds to our understanding of the relationship between diabetes, cholesterol and healthy brain function. If you have diabetes, having tight glycaemic (sugar) control and maintaining a healthy weight are essential to help your overall brain health and to protect against future cognitive decline.

Ryo Suzuki, Kevin Lee, Enxuan Jing, Sudha B. Biddinger, Jeffrey G. McDonald, Thomas J. Montine, Suzanne Craft, C. Ronald Kahn. Diabetes and Insulin in Regulation of Brain Cholesterol Metabolism. Cell Metabolism, Volume 12, Issue 6, 567-579, 1 December 2010 DOI: 10.1016/j.cmet.2010.11.006

A study has just been published in JAMA which found that giving supplements of Omega-3 (DHA) to people with mild to moderate Alzheimer’s disease did not produce any reduction in the rate of cognitive decline, indicating that supplementation in this group would not be warranted.
In this study a group of 402 people with either mild to moderate Alzheimer’s disease, 60% of the group received supplementation of 2 gm of DHA, the other 40% received placebo over an 18-month period. They underwent cognitive testing using the Alzheimer’s Disease Assessment Scale and Clinical Dementia Rating. A sub sample of 102 subjects also underwent functional MRI scanning to look for the rate of cortical atrophy.
The study found no benefit of the supplementation on the ADAS-Cog score or rate of brain atrophy during the time of the trial.
Many people currently take Omega-three’s as a supplement, commonly as fish oil capsules and include fish in their diet on the basis of other studies, which have suggested that this is a way to reduce one’s personal risk of developing dementia or Alzheimer’s disease .
So should we stop doing this?

Absolutely not. The difference here in this study is that they were looking at people who had been already diagnosed with Alzheimer’s.

An earlier study in 2006 at the respected Karolinska Institute had previously looked to see if DHA and EPA (Omega-3) supplements given to a group of people with either diagnosed Alzheimer’s disease or a small sub-group with very early cognitive impairment would be useful as a means of slowing the progression of the disease. This study also found no benefit of supplementation in those already diagnosed with Alzheimer’s.
However those who only had mild cognitive impairment did show some benefit. They had less cognitive decline on mental testing than a control group over a 6-month period, and when the control group received the supplements over a second 6-month period their rate of decline decreased as well. Here the authors proposed that is may be because the omega-3 fatty acids exert an anti–inflammatory effect. Inflammation is believed to be part of the neuropathological development of Alzheimer’s. The comment then was perhaps the anti-inflammatory effect of the Omega-3’s could only be of use prior to too much neuropathological change being evident.
The 2006 study only included a very small number of subjects (32 people) Larger studies with bigger cohorts of those with mild cognitive impairment as well as those at risk of Alzheimer’s are needed to see if Omega 3-s may be of benefit in halting the earlier progression of the disease.
The conclusion from the latest study supports the literature that supplementation with DHA is not beneficial in established mild to moderate Alzheimer’s.

Meanwhile there is plenty of evidence to support continuing to enjoy eating fish and taking Omega-3 supplements as a means of reducing our relative risk of developing cognitive decline and dementia.

Bon appetit!

Journal References:
1. K. Yaffe. Treatment of Alzheimer Disease and Prognosis of Dementia: Time to Translate Research to Results. JAMA: The Journal of the American Medical Association, 2010; 304 (17): 1952 DOI: 10.1001/jama.2010.1625
2. J. F. Quinn, R. Raman, R. G. Thomas, K. Yurko-Mauro, E. B. Nelson, C. Van Dyck, J. E. Galvin, J. Emond, C. R. Jack, M. Weiner, L. Shinto, P. S. Aisen. Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial. JAMA: The Journal of the American Medical Association, 2010; 304 (17): 1903 DOI: 10.1001/jama.2010.1510
3. JAMA and Archives Journals (2006, October 11). Omega-3 Fatty Acids May Slow Cognitive Decline In Some Patients With Very Mild Alzheimer’s Disease. ScienceDaily. Retrieved November 4, 2010, from http://www.sciencedaily.com¬ /releases/2006/10/061010022736.htm

Are we getting more intelligent?

That’s a question I’m sure we would all like to assume to be answered with a “Yes”. However is there any proof of this?

Well it turns out that in Sweden there has been an ongoing study doing intelligence tests on 70 year olds and the findings do actually show that, yes the 70 year olds of today do perform better in these tests than their predecessors of thirty years ago.

And there are probably a number of contributing factors such as
• Improved pre and neonatal care
• Improved nutrition
• Better quality of education
• Better treatment of hypertension and other vascular diseases
• Higher intellectual requirements of today’s society with access to advanced technology, the Internet and television.

But that wasn’t the main reason for conducting this study.
What the researchers were looking for was to see if they could find a better way to predict who is most likely to develop dementia and whether the early symptoms have changed over recent generations.

One thing that the study did reveal too is that the incidence of dementia has remained unchanged over this period of 30 years.
People aged 70 to 75 today have the same incidence of dementia as those of that age group 30 years ago. This is important because with the expected explosion of people likely to be diagnosed with Alzheimer’s disease over the next forty years, it would be possible to assume that Alzheimer’s is becoming more common. The increase is actually simply a reflection of the larger proportion of people in our society reaching that age.

In this study of over 2000 people the only predictor of dementia was found to be those with memory problems. But not all of those with memory problems went on to develop dementia.

The researchers were looking to identify those at risk of developing dementia and while they found pointers for a group born in 1901-1902 the same tests did not reveal any clues for the generation born in 1930. It is hoped that finding earlier signs of dementia will enable people more at risk to get diagnosed earlier and receive support more quickly.

S. Sacuiu, D. Gustafson, M. Sjogren, X. Guo, S. Ostling, B. Johansson, I. Skoog. Secular changes in cognitive predictors of dementia and mortality in 70-year-olds. Neurology, 2010; 75 (9): 779 DOI: 10.1212/WNL.0b013e3181f0737c

This week Bryce Vissel from the Sydney Garvan Institute of Medial Research was on ABC radio discussing the results of the study that had been published in the 29th September edition of PLoS One.

Researchers from Australia and the States have identified a new way that the brain can create memories and store information. The implication of this is that this new pathway may prove useful to provide new and alternative ways of treatments where there has been brain injury or death, such as with stroke and Alzheimer’s disease.

The way our brain works to store memories involves the hippocampus where an essential mechanism called the NMDA receptor is involved. When the NMDA receptor is activated, calcium is allowed to enter the brain cell, which then triggers further molecular reactions resulting in our brain being able to process, store and recall information.
Our understanding over the last twenty or thirty years has been that learning could not take place without these receptors. The scientists were looking to replicate the mechanism artificially and coincidentally uncovered an existing second system that the brain already has in place. In this second system a different receptor called AMPA does the job of encoding memory, but appears only to be activated when the information received is similar to something we have previously learnt. This is called second learning.

The questions now being raised from this finding is to work out what causes this second mechanism to operate. Then it may be possible to look for ways to get it to take over the role of the NMDA mechanism if that isn’t working because of disease or injury.
It might then be used to protect us against conditions such as Alzheimer’s (where the ability to form new memories is lost), because it could be that stimulation of this alternative pathway would then help us to keep participating in memories.
The other potential implication of this finding is that having this second means of learning could have really important effects on how we approach teaching in the classroom in the future as well.

Ref: A Role for Calcium Permeable AMPA Receptors in Synaptic Plasticity and Learning.
Wiltgen BJ, Royle GA, Gray EE, Abdipranoto A, Thangthaeng N, et al. 2010 A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning. PLoS ONE 5(9): e12818. doi:10.1371/journal.pone.0012818