Researchers at Lund University in Sweden headed by Professor Singerup Linse and Erik Helistrand have recently identified a molecular mechanism behind the crucial step in Alzheimer’s that leads to the death of brain cells.
The neurological disease is associated, as a general statement, with memory loss and changes in personality.  The research at Lund helps identify on a molecular level the chemical reactions which cause plaque, a major benchmark in the progression of the disease, to form.   Amyloid beta in its soluble form, found naturally within the brain, acts as a building block and turns into plaque called amyloid fibrils, though the exact pathways of these reactions remain unclear.  An early section of the process of formation of fibrils is two small protein fragments of amyloid beta coming together within a nucleus of a cell to form a fibril.  Lund University’s study suggests that fibrils have a catalytic surface, allowing reactions to happen quicker while touching them, creating new nuclei which in turn aid the proliferation of more fibrils, causing exponential growth in plaque formation.  After a small but crucial amount of amyloid fibrils are created, more immediately surface to begin a self-perpetuating process key to understanding Alzheimer’s.  These findings dash what was previously believed; that fibrils formed in single nuclei reactions as a uniform process.  More profound perhaps than the catalytic surface is the discovery that this aggregation of amyloid fibrils creates toxic oligomers, small groups of proteins.  These oligomers have been identified as neurotoxins that play a significant part in cell-death.
It is the hope of Professor Linse that new medicines targeted at shutting down the catalyzation of amyloid fibrils and the resultant neurotoxins can slow or even stop the progression of the disease. For now, it is heartening that ongoing Alzheimer’s research is yielding new information about the degenerative disease and possible ways to fight its progression.

1)  S. I. A. Cohen, S. Linse, L. M. Luheshi, E. Hellstrand, D. A. White, L. Rajah, D. E.  Otzen, M. Vendruscolo, C. M. Dobson, T. P. J. Knowles. Proliferation of amyloid- 42 aggregates occurs through a secondary nucleation mechanism. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218402110
2) Lund University (2013, May 29). Molecular chain reaction in Alzheimer’s disease. ScienceDaily. Retrieved May 30, 2013, from http://www.sciencedaily.com /releases/2013/05/

Keywords: Alzheimer’s disease, Amyloid Beta Protein

Article By: Lauren Horne (edited by Emma Henson)

Roskamp Institute is devoted to find cure for brain related disorders. Its a non-profit research institute located at Sarasota, Florida. Dr. Michael Mullan is the head and CEO of the Roskamp Institute.

Recently, there has been increasing interest in the role of sports head injuries and subsequent cognitive decline. For instance, American football players are being scrutinized more closely because of new research suggesting close links between repeated concussion and decline in cognitive abilities.

Complaints by professional players are now being taken seriously, as associations all over the country begin to take action.

“I’ve had times where I walked up to the line, where I know the play, but don’t know what to do.” – Oakland Raiders tight end Tony Stewart

“I’ve known of players hiding concussions..Sometimes players aren’t real sure.  They hit their head, they get a little cuckoo for a little while.  It happens all the time.” – Kansas City Chiefs center Rudy Niswanger

Over the last three decades, there has been much work on the relationship between head injury (usually single head injury) and Alzheimer's disease (AD) and other dementias. Many well designed, population based studies have suggested a link between head injury and the development of AD and other dementias. However, there are many discrepancies between these studies and the risk attributed to head injury has varied widely between them. Several key factors are often examined in these studies to try to understand better the relationship between traumatic brain injury (TBI) and AD.

The following areas have been studied extensively:

1.      The Gender Effect:  Despite the many case control and cohort studies, none have shown an increased risk for AD after TBI for women. Although many TBI studies focus on the male population who are more at risk (for instance, in contact sports or in the military) the finding that women are at no increased risk of AD after TBI suggests that there may be a protective effect of female hormones against the development of AD after head injury.

2.      The degree of injury and subsequent development of AD or related disorders: Few studies have adequately assessed the degree of injury and so information in this area is limited but, the studies that have, in general, suggest that more moderate or severe injuries predispose to dementia later in life. For instance, one study divided TBI into mild, moderate, and severe categories:  injuries with loss of consciousness (LOC) or post-traumatic amnesia (PTA) of less than 30 minutes (mild); of more than 30 minutes but less than 24 hours (moderate); and of more than 24 hours (severe). Most studies suggested moderate and severe disease is more related to AD and that full recovery of cognitive loss can be regained after mild TBI.

3.      Time of injury to the development of subsequent dementia:  This relationship has been studied in large populations and there are good data to suggest that TBI in old age is associated with worsening of outcome compared to TBI at a younger age. Nevertheless, even individuals that have TBI in early adulthood (if the injury is severe enough) are at increased risk of AD and other dementias as many as five decades later.

One key question is how the brain "remembers" the injury for so many years and why there may be no signs of cognitive impairment soon after the injury for many decades until AD onsets. The question of the molecular underpinnings of TBI and how the brain continues to register that an injury has occurred is an area of intense study.

One such candidate for molecular memory is amyloid.  The amyloid molecule is increased in the brains of AD sufferers and occurs early in the pathological sequence that leads to full-blown AD. Most studies show that only about one-third of TBI victims have amyloid at autopsy.  Although amyloid is produced acutely after TBI, much of that amyloid does not stay in the brain but is degraded in the weeks and months following injury.

Another pathological molecule central to the AD process is tau.  Tau protein is formed when neurons die.  Although tau has been implicated in TBI, again, there are inconsistent data between studies -- some showing no increased involvement of tau while others show hyperphosphorylation and/or aggregation of tau. More recently in repetitive head injury (for instance, those occurring in American football) tau has been implicated as it has been seen particularly around blood vessels in the brain.

Whatever the ultimate underlying cause of the link between TBI and the subsequent development of AD, we can expect that once those links are fully uncovered, they will become new targets for the prevention of AD following TBI.

One other area that deserves attention is the genetic risk for poor recovery after TBI and subsequent risk for AD. Although it is generally accepted that APOE4 is a risk factor for AD, some studies of head injury have been equivocal in demonstrating that APOE4 acts synergistically with TBI to increase risk for AD.

However, given the plethora of data on the negative roles of APOE4 in the brain after TBI, it is safe to assume that individuals who carry the E4 are most probably at greater risk for developing AD than those who do not. It has been advocated that those individuals carrying an APOE4 allele should not engage in professions or pastimes with increased risk of TBI.

Much more work is needed in this area; but, at this stage, as a precaution, this is probably a position that can be easily endorsed.

Dr. Michael Mullan is the president of Sci-Brain. A company providing personalized program to reduce risk of Alzheimer's disease and improve your Brain Health.

Recent studies in at this month’s Alzheimer’s Association International Conference in Vancouver, Canada has shown that the way a person walks is linked to cognitive function. That is, the speed and style by which a person walks correlates with cognitive changes that may eventually lead to the development of Alzheimer’s disease (AD). Signs of cognitive failure include walking at a slower pace, and fluctuated or uncontrolled walking. Usual studies of AD involve patients who do not move, but the thinking capabilities of the human brain have a strong relationship with its movement skills. While research for the link between walking and mental function has been going on for the past decade, it has been recently taken into new heights because these studies have revealed more specifics about the relationship. For example, the variation and pace in walking is linked with a person’s ability to plan and organize, while rhythm is associated with the speed by which information is processed. The decline in cognitive functions has a parallel relationship with a decrease in walking speed. Newer studies have been incorporated more detailed and advanced approaches than previous research in terms of measuring changes in gait, such as making the participants multitask or having them use electronic walkways.  These studies may lead to a new method in which symptoms of AD can be detected earlier on, as to prevent the development of the disease. It also reinforces the idea that dementia can be delayed with an activity that should be common to humankind, exercise.

For further details on these studies and on Alzheimer’s disease, please visit:



Keywords: Alzheimer’s disease; walking; exercise; cognitive functions

Wendy Liu

July 24, 2012