Category: Alzheimer’s

An international research team led by the Spanish National Research Council (CSIC) and researchers from Kiel University revealed the atomic‐level structure of the human peptidase enzyme meprin β (beta). The enzyme is related to inflammation, cancer and Alzheimer's Disease and is involved in cellular proliferation and differentiation. The knowledge of the enzyme structure will allow for the development of a new medication type different from those known up to now.

The study was published in the current issue of the Proceedings of the National Academy of Sciences.

"Now that we know how meprin β looks, how it works and how it relates to diseases, we can search for substances that stop its enzyme activities when they become harmful," explains Xavier Gomis-Rüth, researcher at the Molecular Biology Institute of Barcelona, who led the project. Meprin β is an enzyme that is anchored in the outer wall of cells. Its normal function in the human metabolism is to cut off certain proteins, e.g. growth factors, that are also anchored in the cell wall. In this way meprin β releases protein fragments into the environment surrounding the cells — a natural and normal process, as long as it occurs at a certain intensity. However, under specific circumstances, meprin β may function abnormally, and, for example, releases too many protein fragments. The protein pieces than overdo their natural task in the cell surroundings, causing disorder in the human body. Such disorder typically occurs when inflammation, cancer or Alzheimer's Disease get started.

In their study, the scientists found out that meprin β consists of two identical molecules building a dimeric structure with a cleft in the middle. "We also discovered that the active site cleft is something like the scissor of the enzyme, the actual place where the proteins are cleaved," explains Christoph Becker-Pauly, researcher at the Institute of Biochemistry at Kiel University, and principle investigator of the Kiel Collaborative Research Center 877 „Proteolysis as a Regulatory Event in Pathophysiology." Molecular biologist Gomes-Rüth points out to the next research goal: "We now need to find a substance that fits right into the cleft and will thus block the cleaving activity of meprin β." Such a substance could be the key to new therapeutical drugs against inflammation, cancer or Alzheimer's Disease.

The research has been carried out in collaboration with scientists from Max Planck Institute for Biochemistry and Johannes Gutenberg University Mainz (Germany) as well as University of Bern (Switzerland).

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Journal Reference:

1. J. L. Arolas, C. Broder, T. Jefferson, T. Guevara, E. E. Sterchi, W. Bode, W. Stocker, C. Becker-Pauly, F. X. Gomis-Ruth. Structural basis for the sheddase function of human meprin   metalloproteinase at the plasma membrane. Proceedings of the National Academy of Sciences, 2012; 109 (40): 16131 DOI: 10.1073/pnas.1211076109

 The mice in which scientists expected to test treatments for Lou Gehrig's disease turn out to have problems that could slow research, reported Alzforum, a research news site specializing in Alzheimer's and related diseases. To the researchers' surprise, the mice didn't die of the spinal nerve disease. Instead, they succumbed to intestinal blockage.

"There were high expectations," said Robert Baloh of the Cedars-Sinai Medical Center in Los Angeles, who made the new mice. "The problem is, they are still mice. Humans and mice, even if they have the same genetic mutation, get different diseases."

Between 20,000 and 30,000 people in the U.S. have Lou Gehrig's disease, or amyotrophic lateral sclerosis, which kills nerve cells in the spine. It causes paralysis and death, typically within a few years. There is only one treatment, riluzole, which extends live by a couple of months.

Difficulties in transferring treatments from mice to people have long plagued scientists trying to treat Lou Gehrig's and Alzheimer's. That's why researchers were excited when, five years ago, it was discovered that some people with Lou Gehrig's have mutations in a gene called TDP-43. They rushed to make mice with the same mutations, thinking the animals would be an excellent new testing ground.

But problems, such as the intestinal blockage, are arising as scientists work to fully understand the new mice. Nonetheless, the mice could still be useful in testing drugs and should also help researchers understand just how Lou Gehrig's kills nerve cells, experts say. And in the process, scientists are learning just how rigorously they have to characterize a given mouse model, and design treatment studies in those mice, to then have a fair shot at success in the clinic.

Alzheimer's disease is a severe neurodegenerative disease that affects 45% of people over 85 years of age. The research teams of Prof. Jin-Moo Lee at Washington University in Saint Louis, USA, and Prof. Milos Pekny at Sahlgrenska Academy in Gothenburg, Sweden, have identified astrocytes as a novel target for the development of future treatment strategies.

The results have just been published in the FASEB Journal.

Astrocytes are known as cells that control many functions of the healthy as well as diseased brain, including the control of regenerative responses.

In patients suffering from Alzheimer's disease, astrocytes in the vicinity of amyloid plaques and degenerating neurons become hyperactive.

Until now, many researchers considered this astrocyte hyperactivity in the brains of Alzheimer's disease patients as negative and contributing to the progression of this devastating disease.

The current study generated groundbreaking data with important implications. The US and Swedish research teams used a mouse model of Alzheimer's disease in which they genetically reduced astrocyte hyperactivity. They found that such mice developed more amyloid deposits and showed more pronounced signs of neurodegeneration than mice with normal response of astrocytes.

This suggests that astrocyte response to the disease process slows down the disease progression.

– We are truly exited about these findings. Now we need to understand the mechanism underlying the beneficial role of hyperactive astrocytes in Alzheimer's disease progression. Understanding this process on a molecular level should help us to design strategies for optimization of the astrocyte response, says Prof. Milos Pekny.

– We see that astrocyte hyperactivity in Alzheimer's disease brains is tightly connected to activation of microglia, the brain's own immune cells. This implies that the two cell types communicate to mediate a coordinated response to disease states, says Prof. Jin-Moo Lee.

This international collaborative team of neuroscientists is pursuing further studies to understand molecular mechanisms by which astrocytes prevent the deposition of amyloid plaques in Alzheimer's disease.

Recent studies have linked caffeine consumption to a reduced risk of Alzheimer's disease, and a new University of Illinois study may be able to explain how this happens.

"We have discovered a novel signal that activates the brain-based inflammation associated with neurodegenerative diseases, and caffeine appears to block its activity. This discovery may eventually lead to drugs that could reverse or inhibit mild cognitive impairment," said Gregory Freund, a professor in the U of I's College of Medicine and a member of the U of I's Division of Nutritional Sciences.

Freund's team examined the effects of caffeine on memory formation in two groups of mice — one group given caffeine, the other receiving none. The two groups were then exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow, and then allowed to recover.

The caffeine-treated mice recovered their ability to form a new memory 33 percent faster than the non-caffeine-treated mice. In fact, caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1 is a critical player in the inflammation associated with many neurodegenerative diseases, he said.

"It's not surprising that the insult to the brain that the mice experienced would cause learning memory to be impaired. But how does that occur?" he wondered.

The scientists noted that the hypoxic episode triggered the release of adenosine by brain cells.

"Your cells are little powerhouses, and they run on a fuel called ATP that's made up of molecules of adenosine. When there's damage to a cell, adenosine is released," he said.

Just as gasoline leaking out of a tank poses a danger to everything around it, adenosine leaking out of a cell poses a danger to its environment, he noted.

The extracellular adenosine activates the enzyme caspase-1, which triggers production of the cytokine IL-1β, a critical player in inflammation, he said.

"But caffeine blocks all the activity of adenosine and inhibits caspase-1 and the inflammation that comes with it, limiting damage to the brain and protecting it from further injury," he added.

Caffeine's ability to block adenosine receptors has been linked to cognitive improvement in certain neurodegenerative diseases and as a protectant against Alzheimer's disease, he said.

"We feel that our foot is in the door now, and this research may lead to a way to reverse early cognitive impairment in the brain. We already have drugs that target certain adenosine receptors. Our work now is to determine which receptor is the most important and use a specific antagonist to that receptor," he said.

The study appears in the Journal of Neuroscience. Co-authors are Gabriel Chiu, Diptaman Chatterjee, Patrick Darmody, John Walsh, Daryl Meling, and Rodney Johnson, all of the U of I. Funding for the study was provided by the National Institutes of Health.

Using animal models, scientists at the Gladstone Institutes have discovered how a protein deficiency may be linked to frontotemporal dementia (FTD) — a form of early-onset dementia that is similar to Alzheimer's disease. These results lay the foundation for therapies that one day may benefit those who suffer from this and related diseases that wreak havoc on the brain.

As its name implies, FTD is a fatal disease that destroys cells, or neurons, that comprise the frontal and temporal lobes of the brain — as opposed to Alzheimer's which mainly affects brain's memory centers in the hippocampus. Early symptoms of FTD include personality changes, such as increased erratic or compulsive behavior. Patients later experience difficulties speaking and reading, and often suffer from long-term memory loss. FTD is usually diagnosed between the ages of 40 and 65, with death occurring within 2 to 10 years after diagnosis. No drug exists to slow, halt or reverse the progression of FTD.

A new study led by Gladstone Senior Investigator Robert V. Farese, Jr., MD, offers new hope in the fight against this and other related conditions. In the latest issue of the Journal of Clinical Investigation, available today online, Dr. Farese and his team show how a protein called progranulin prevents a class of cells called microglia from becoming "hyperactive." Without adequate progranulin to keep microglia in check, this hyperactivity becomes toxic, causing abnormally prolonged inflammation that destroys neurons over time — and leads to debilitating symptoms.

"We have known that a lack of progranulin is linked to neurodegenerative conditions such as FTD, but the exact mechanism behind that link remained unclear," said Dr. Farese, who is also a professor at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "Understanding the inflammatory process in the brain is critical if we are to develop better treatments not only for FTD, but for other forms of brain injury such as Parkinson's disease, Huntington's disease and multiple sclerosis (MS) — which are likely also linked to abnormal microglial activity."

Microglia — which are a type of immune cells that reside in the CNS — normally secrete progranulin. Early studies on traumatic CNS injury found that progranulin accumulates at the injury site alongside microglia, suggesting that both play a role in injury response. So, Dr. Farese and his team designed a series of experiments to decipher the nature of the relationship between progranulin and microglia.

First, the team generated genetically modified mice that lack progranulin. They then monitored how the brains of these mice responded to toxins, comparing this reaction to a control group.

"As expected, the toxin destroys neurons in both sets of mice — but the progranulin-deficient mice lost twice as many neurons as the control group," said Lauren Herl Martens, a Gladstone and UCSF graduate student and the study's lead author. "This showed us that progranulin is crucial for neuron survival. We then wanted to see whether a lack of progranulin itself would injure these cells — even in the absence of toxins."

In a petri dish, the researchers artificially prevented microglia from secreting progranulin and monitored how these modified microglia interacted with neurons. They observed that a significantly greater number of neurons died in the presence of the progranulin-deficient microglia when compared to unmodified microglia.

Other experiments revealed the process' underlying mechanism. Microglia are the CNS's first line of defense. When the microglia sense toxins or injury, they trigger protective inflammation — which can become toxic to neurons if left unchecked. Dr. Farese's team discovered that progranulin works by tempering the microglia's response, thereby minimizing inflammation. Without progranulin, the microglia are unrestricted — and induce prolonged and excessive inflammation that leads to neuron damage — and can contribute to the vast array of symptoms that afflict sufferers FTD and other fatal forms of brain disease.

"However, we found that boosting progranulin levels in microglia reduced inflammation — keeping neurons alive and healthy in cell culture," explained Dr. Farese. "Our next step is to determine if this method could also work in live animals. We believe this to be a therapeutic strategy that could, for example, halt the progression of FTD. More broadly, our findings about progranulin and inflammation could have therapeutic implications for devastating neurodegenerative diseases such as Alzheimer's, Parkinson's and MS."

Other scientists who participated in this research at Gladstone include Sami Barmada, PhD, Ping Zhou, MD, Li Gan, PhD and Steve Finkbeiner, MD, PhD. Funding came from a variety of sources, including the Consortium for Frontotemporal Dementia Research, the ALS Association and the National Institutes of Health.

Groundbreaking research taking place at the University of York could lead to Alzheimer's disease being diagnosed in minutes using a simple brain scan.

Scientists are working on new technology that could revolutionise the way in which Magnetic Resonance Imaging (MRI) scans are used to view the molecular events behind diseases like Alzheimer's, without invasive procedure, by increasing the sensitivity of an average hospital scanner by 200,000 times.

The technology underpinning this project, SABRE (Signal Amplification by Reversible Exchange), has received a £3.6m Strategic Award from the Wellcome Trust to fund a team of seven post-doctoral researchers from this month.

The new grant brings the total support for SABRE from the Wellcome Trust, the Wolfson Foundation, Bruker Biospin, the University of York and the Engineering and Physical Sciences Research Council (EPSRC) to over £12.5m in the last three years.

A new Centre for Hyperpolarisation in Magnetic Resonance (CHyM) is being purpose-built at York to house the project. The building, which is nearing completion at York Science Park, includes a chemical laboratory, four high field nuclear magnetic resonance systems and space for 30 research scientists.

The SABRE project is led by Professor Simon Duckett, from the Department of Chemistry at York, Professor Gary Green, from the York Neuroimaging Centre (YNiC) and Professor Hugh Perry, from the Centre for Biological Sciences, University of Southampton.

Professor Duckett said: "While MRI has completely changed modern healthcare, its value is greatly limited by its low sensitivity. As well as tailoring treatments more accurately to the needs of individual patients, our hope is that in the future doctors will be able to accurately make diagnoses that currently take days, weeks and sometimes months, in just minutes."

Professor Green added: "SABRE has the potential to revolutionise clinical MRI and related MR methods by providing a huge improvement in the sensitivity of scanners. This will ultimately produce a step change in the use and type of information available to scientists and clinicians through MRI, allowing the diagnosis, treatment and clinical monitoring of diverse neurodegenerative diseases."

The Centre for Hyperpolarisation in Magnetic Resonance will be officially opened by Sir William Castell, Chairman of the Wellcome Trust, in September 2013.

The Centre brings together scientists from a range of backgrounds including Chemistry, Psychology, Biology and the Hull York Medical School. Recent appointments include British neuroscientist Professor Miles Whittington and Dr Heidi Baseler, a lecturer in specialist medical imaging from the USA. Professor Jüergen Hennig of the University Hospital Freiburg, one of the world's leading experts in the medical application of MRI technology, is also associated with the Centre.

The Centre for Hyperpolarisation in Magnetic Resonance was created to build on an exciting breakthrough in the use of hyperpolarisation in MRI by scientists from the York Neuroimaging Centre (YNIC) and the York Magnetic Resonance Centre (YMRC).

Hyperpolarisation involves the transfer of magnetism from parahydrogen to molecules making them more visible in MRI scans. The Centre's SABRE programme will develop the chemical basis of this method to make it suitable for medical applications.

Rember® — the blue dye that created a stir in 2008 when Phase 2 clinical trial data claimed that it slowed decline in people with Alzheimer's disease — has now been revamped for Phase 3 testing in another disease, behavioral-variant frontotemporal dementia (bvFTD).

TauRx Therapeutics, a Singaporean-Scottish biotech company, reformulated Rember® to improve absorption and tolerability, and will test its modified oral compound, LMTX, in bvFTD patients at 25 to 30 sites worldwide. Pending ethics review and approvals, the 12-month bvFTD trial is expected to begin enrolling in November or December. The company also plans to launch two Phase 3 trials in AD in late 2012.

The TauRx molecule has roused researchers' curiosity on a number of fronts. It is believed to be the only drug in clinical testing that breaks up aggregates of tau, the protein that forms neurofibrillary tangles in Alzheimer's and other neurodegenerative diseases. Even more unusual, it has reached Phase 3 with hardly any published preclinical data. Aside from several talks and posters presented at the International Conferences on Alzheimer's Disease in Chicago and Vienna, which Alzforum reported in 2008 and 2009, very little data on Rember or LMTX is in the public domain. Moreover, scientists had concerns about the design and analysis of the company's earlier Phase 2 trial in AD, some of which are addressed in the upcoming Phase 3 studies. A recent Alzforum story and Q&A with TauRx CEO Claude Wischik describe these developments.

Psychologists at the University of Toronto and the Georgia Institute of Technology — commonly known as Georgia Tech — have shown that an individual's inability to recognize once-familiar faces and objects may have as much to do with difficulty perceiving their distinct features as it does with the capacity to recall from memory.

A study published in the October issue of Hippocampus suggests that memory impairments for people diagnosed with early stage Alzheimer's disease may in part be due to problems with determining the differences between similar objects. The research contributes to growing evidence that a part of the brain once believed to support memory exclusively — the medial temporal lobe — also plays a role in object perception.

"Not only does memory seem to be very closely linked to perception, but it's also likely that one affects the other," said Morgan Barense of the University of Toronto's Department of Psychology. "Alzheimer's patients may have trouble recognizing a loved one's face not just because they can't remember it but also because they aren't able to correctly perceive its distinct combination of features to begin with."

The research team tested patients with mild cognitive impairment (MCI) — a disorder commonly thought to be a precursor to Alzheimer's disease — on their ability to determine whether two rotated side-by-side pictures were different or identical.

In one set of trials, many pairs of photos of blob-like objects were shown. These were classified as high-interference trials as the photos varied only slightly when they weren't a perfect match, either by shapes or fill pattern. As expected, MCI patients struggled greatly to identify identical pairings.

In low-interference trials, the blob-like objects were interspersed with photos in which non-matches were more extreme and varied widely. For example, a picture of a butterfly was shown next to a photo of a microwave. Interspersing the very similar blob-like objects with photos of dissimilar objects greatly reduced the amount of interference.

"Minimizing the degree of perceptual interference improved patients' object perception by reducing the number of visually similar features," said lead author of the study Rachel Newsome, a PhD candidate in U of T's Department of Psychology.

The findings suggest that, under certain circumstances, reducing "visual clutter" could help MCI patients with everyday tasks. For example, buttons on a telephone tend to be the same size and color. Only the numbers are different — a very slight visual difference for someone who struggles with object perception. One solution could be a phone with varying sized buttons and different colors.

The researchers, which also included Georgia Tech psychology professor Audrey Duarte, administered the same tests to people at risk for MCI who had previously shown no signs of cognitive impairment.

"They performed the same as those with MCI, suggesting that the perception test could be used as an early indicator of cognitive impairment," said Barense. "It provides further support for the idea that any damage to a small area of the medial temporal lobe — especially the perirhinal cortex — affects perception as much as it does memory."

The study is reported in the paper "Reducing perceptual interference improves visual discrimination in mild cognitive impairment: Implications for a model of perirhinal cortex function" in the October special edition of Hippocampus titled Perirhinal Cortex: At the Crossroads of Memory and Perception. Funding for the research was provided by the Canadian Institutes for Health Research. It builds on previous research done by Barense and colleagues that tested the perception abilities of individuals suffering from amnesia.

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Journal Reference:

1. Rachel N. Newsome, Audrey Duarte, Morgan D. Barense. Reducing perceptual interference improves visual discrimination in mild cognitive impairment: Implications for a model of perirhinal cortex function. Hippocampus, 2012; 22 (10): 1990 DOI: 10.1002/hipo.22071

The unexpected survival of embryonic neurons transplanted into the brains of newborn mice in a series of experiments at the University of California, San Francisco (UCSF) raises hope for the possibility of using neuronal transplantation to treat diseases like Alzheimer's, epilepsy, Huntington's, Parkinson's and schizophrenia.

 

The experiments, described this week in the journal Nature, were not designed to test whether embryonic neuron transplants could effectively treat any specific disease. But they provide a proof-of-principle that GABA-secreting interneurons, a type of brain cell linked to many different neurological disorders, can be added in significant numbers into the brain and can survive without affecting the population of endogenous interneurons.

The survival of these cells after transplantation in numbers far greater than expected came as a shock to the team, which was led by UCSF professor Arturo Alvarez-Buylla, PhD, and former UCSF graduate student Derek Southwell, MD, PhD.

The prevailing theory held that the survival of developing neurons is something like a game of musical chairs. The brain has limited capacity for these cells, forcing them to compete with each other for the few available slots. Only those that find a place to "sit" (and receive survival signals derived from other cell types) will survive when the music stops. The rest die a withering death.

Based on this theory, the UCSF team had expected only a fixed and small number of transplanted embryonic interneurons would survive in the brains of older recipient mice, regardless of how many they transplanted. What they found was very different: Regardless of how many they transplanted, a consistent percentage always survived.

"[This constant rate of survival] suggests that these cells, which other collaborative studies have shown have great therapeutic promise, can be added to cortex in significant numbers," said Alvarez-Buylla, who is the Heather and Melanie Muss Professor of Neurological Surgery and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Past work at UCSF and elsewhere has shown that transplanting these cells can create a new critical period of plasticity in the recipient brain, reduce seizures in animal models of epilepsy, and reduce Parkinson's-like movement disorders in laboratory rats. The activity of these cells is often disrupted in Alzheimer's disease, and their number is altered in the brains of people with schizophrenia. When transplanted into the spinal cord, they also help decrease pain sensation.

In the current study, the UCSF team found that as they altered the number of cells they transplanted, a constant proportion of these cells survived — rather than a constant number — suggesting that a fraction of the cells is destined to die by cell-autonomous mechanisms or that a survival factor is secreted by the inhibitory neurons themselves. The work shows that these interneurons may be transplanted in far greater numbers than previously thought — an observation that could have important implications for the use of these cells to correct defects in the excitatory/inhibitory valance in the disease brain.

Survival of Cells Depends on Unknown Signals

GABAergic interneurons are essential for brain function because they balance the action of "excitatory" neurons in the cerebral cortex by producing inhibitory signals. Diseases like epilepsy, Alzheimer's, Huntington's, Parkinson's and schizophrenia are all variously linked to disruptions in this excitatory/inhibitory balance, and problems with the GABAergic interneurons have been documented in all these diseases.

These GABAergic interneurons are not born in the cerebral cortex — the part of the brain where they will ultimately become incorporated into functional circuits. Instead, they are created in a distant part of the developing brain and then migrate to their final destination. For decades, scientists have not known how the appropriate number of these interneurons is determined, how many are formed, when they die and how many survive after reaching the cerebral cortex. The recent publication addresses some of these unknowns, but also revealed an unexpected observation.

It is generally believed that neuronal numbers are determined by availability of survival signals provided by other target cells. This idea, generally known as the "neurotrophic hypothesis," is based on Nobel Prize-winning experiments in the 1940s showing how the survival of developing neurons in the spinal cord and peripheral nervous system is determined. That work showed that only the nerve fibers that could correctly connect to targets outside the nervous system would survive and that these targets produced a protein called nerve growth factor responsible for keeping the nerves alive.

For many years, the neurotrophic hypothesis has dominated ideas of how and why cells in the brain live and die. "The neurotrophic hypothesis has since been assumed to apply to all types neurons and all areas of the nervous system," said Southwell.

The assumption was that once the GABAergic interneurons winded their way to the right part of the brain, only those that melded with the other neurons already there would be protected by a protein or some other factor to stay alive. Instead, the survival of the transplanted interneurons was determined in a manner that was independent from competition for survival signals produced by other types of cells in the recipients.

While the new experiments do not overthrow this theory as it applies to how nerves outside the brain connect to their targets, they suggest there may be something else going on with GABAergic interneurons.

This work was funded by the California Institute for Regenerative Medicine, the John G. Bowes Research Fund, the Spanish Ministry of Science and Innovation, and the National Institute of Neurologic Disorders and Stroke, one of the National Institutes of Health, through grant #R01 NS071785 and # R01 NS048528.

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Journal Reference:

1. Derek G. Southwell, Mercedes F. Paredes, Rui P. Galvao, Daniel L. Jones, Robert C. Froemke, Joy Y. Sebe, Clara Alfaro-Cervello, Yunshuo Tang, Jose M. Garcia-Verdugo, John L. Rubenstein, Scott C. Baraban, Arturo Alvarez-Buylla. Intrinsically determined cell death of developing cortical interneurons. Nature, 2012; DOI: 10.1038/nature11523

Researchers at Western University have created a mouse model that reproduces some of the chemical changes in the brain that occur with Alzheimer's, shedding new light on this devastating disease. Marco Prado, Vania Prado and their colleagues at the Schulich School of Medicine & Dentistry's Robarts Research Institute, looked at changes related to a neurotransmitter or chemical messenger, named acetylcholine (ACh), and the kinds of memory problems associated with it.

The research is now published online by PNAS.

The researchers, including first author Amanda Martyn, created a mouse line that doesn't have enough ACh being secreted by neurons in the same brain regions affected by Alzheimer's disease. They found this neurochemical failure caused problems with spatial memory, the stored information that is needed for navigating one's environment. For instance, the memory needed to drive across town. They also found the reduction of ACh led to hyperactivity, which many patients with Alzheimer's experience.

"Once we reproduced that neurochemical failure, we asked, 'how does that affect spatial memory, how does it affect learning?' We found mice that don't have that particular chemical messenger in specific areas of the brain, have problems with spatial memory, for example," says Marco Prado. "This reveals specific types of cognitive deficits that we can hope to improve with drugs that boost this chemical messenger."