In recent years it became clear that people with diabetes face an ominous prospect – a far greater risk of developing Alzheimer’s disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases.
They found that the gene, known to be present in many Alzheimer’s disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases.
‘People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy,’ said Professor Li, explaining why the link is not far-fetched.
Although the cause of Alzheimer’s is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients’ brains.
Mutations in the human ‘amyloid precursor protein’ (APP) gene, or in genes that process APP, show up in cases of Alzheimer’s that run in families. In the study, Professor Li and her colleagues scrutinised a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer’s disease gene.
‘What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted,’ said Professor Li. ‘We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway.’
This suggested that the human version of the gene likely plays a role in both Alzheimer’s disease and diabetes.
They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked.
The APL-1 is so important, they found, that ‘when you knock out the worm-equivalent of APP, the animals die,’ Li explained. ‘This tells us that the APP family of proteins is essential in worms, as they are essential in mammals,’ like us.
Professor Li and her colleagues hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer’s disease and diabetes. The City College of New York.

An international team of researchers have developed a new method for measurement of aggregated beta-amyloid – a protein complex believed to cause major nerve cell damage and dysfunction in Alzheimer’s disease. The new method might facilitate diagnosis and detection as well as development of drugs directed against aggregated beta-amyloid.
Alzheimer’s disease (AD) is the most common cause of memory decline and dementia. According to the Alzheimer World Report 2011, today around 36 million people suffer from Dementia (around 20 – 25 million are Alzheimer’s patients). These numbers will dramatically increase with the ageing populations over the next few decades. For the year 2050 the expected number of dementia patients will be 115 – 200 million (70 – 150 million Alzheimer’s cases). It is therefore important to develop new therapies and diagnostic methods to detect and treat this complex chronic neurodegenerative brain disease.
Alzheimer’s disease is characterised by aggregates in the brain, containing a protein called beta-amyloid. The neuropathology of Alzheimer’s disease has recently been linked to the neurotoxic amyloid-β (Aβ) oligomers. The crucial role of Aβ oligomers in the early events of AD is experimentally underlined. Several recent results suggest that those oligomers may cause the death of neurons and neurological dysfunctions relevant to memory. Furthermore Aβ oligomers levels are increased in brain and cerebrospinal fluid samples from people with Alzheimer’s disease. This reflects the potential of Aβ oligomers as a marker for the early diagnosis of the disease.
An international team of scien
He analysed the cerebrospinal fluid of 30 neurological patients, including 14 Alzheimer’s patients. ‘These samples provided from leading expert academic memory clinics in Germany and Sweden are of the best quality and are highly characterised in order to provide robust and reliable results on promising novel biomarker candidates’, Professor Harald Hampel of Frankfurt University, a lead investigator comments.
‘Because of the limited number of samples, however, further study is needed to confirm the results,’ said Dr. Oskar Hansson of Lund University. The study was an international co-operation with the University of California in the U.S., the Goteborg and Malmö Universities from Sweden and the University of Frankfurt in Germany.
The test might not only be used fo
tists from Germany, Sweden and the U.S. have used a new method to quantify soluble variants of aggregated beta-amyloid (Aβ oligomers) in cerebrospinal fluid by flow cytometry. "We found that patients with a greater number of Aβ oligomers in the cerebrospinal fluid had a more pronounced disease," says Dr. Alexander Navarrete Santos (the developer of this method and now employee of the Research Laboratory of the University of Halle, Department of Cardiothoracic Surgery), and first author of the study.r the early detection of AD but can also be used when developing new and effective therapies for AD. A decline in the number of Aβ oligomers in cerebrospinal fluids could be a hint for the effectiveness of new drug therapies. EurekAlert

Scientist Howard Young’s research has taken a dramatic, unexpected turn in the last few months, thanks to a serendipitous chain of events that could lead to a genetic test that can predict heart failure in certain people before it happens.
It started when members of his team, Delaine Ceholski and Cathy Trieber, discovered a new mutation in a protein called phospholamban, which they predicted would cause the heart to be less responsive to changes in the body and eventually lead to heart failure. One month after submitting their for review, their work was validated when – in completely separate research – the mutation was found in two patients in Brazil.
‘We predicted it exactly,’ said Young, an associate professor in the Faculty of Medicine & Dentistry’s Department of Biochemistry and researcher at the National Institute for Nanotechnology. ‘It’s interesting, because as basic researchers you feel like you have to constantly defend your research and how relevant test-tube work is to patients… and then one day, to our surprise, we were right.
‘I expected to be right, but not in the time frame that occurred. It happened quickly.’
Shortly after that, Young was asked to speak at the Centennial Lectures, a speakers series offered by the faculty as a lead-up to the medical school’s centennial year in 2013 to spotlight the translational work of its researchers.
Young was paired with cardiologist and researcher Justin Ezekowitz of the Department of Medicine. Each became interested in the work of the other, and now the two are pairing up to screen patients’ blood samples for mutations in the phospholamban protein.
‘If someone had asked me last September if we’d ever get into sequencing patients’ genes and trying to discover mutants, I would say ‘no, you’re wrong,’ ‘ said Young. ‘But now we’re very interested in starting large sequencing studies to try and find more mutations.’
Through his research, Young thinks he has established good prediction models for heart disease. If his research group finds a mutation in phospholamban through blood screening, Young believes he can predict the severity of the mutation and whether or not it will be associated with disease.
‘It will be truly personalised medicine,’ said Young. ‘If we know they [patients] have a mutation before disease, monitoring and early treatment could improve and extend the quality of life for these patients.’
Young and researchers in his lab will look at blood samples from about 750 patients at the Mazankowski Alberta Heart Institute. Young expects to find at least two or three people with a mutation in phospholamban.
They’ll also look for other mutations that have not been previously discovered. ‘There’s a related protein to phospholamban in the skeletal muscle and the atria of the heart, so we’re branching out and going to see if we can identify new mutations, because no mutations have been identified in that protein,’ he said. University of Alberta Faculty of Medicine & Dentistry

Researchers at Oregon State University have tapped into the extraordinary power of carbon ‘nanotubes’ to increase the speed of biological sensors, a technology that might one day allow a doctor to routinely perform lab tests in minutes, speeding diagnosis and treatment while reducing costs.
The new findings have almost tripled the speed of prototype nano-biosensors, and should find applications not only in medicine but in toxicology, environmental monitoring, new drug development and other fields.
More refinements are necessary before the systems are ready for commercial production, scientists say, but they hold great potential.
‘With these types of sensors, it should be possible to do many medical lab tests in minutes, allowing the doctor to make a diagnosis during a single office visit,’ said Ethan Minot, an OSU assistant professor of physics. ‘Many existing tests take days, cost quite a bit and require trained laboratory technicians.
‘This approach should accomplish the same thing with a hand-held sensor, and might cut the cost of an existing $50 lab test to about $1,’ he said.
The key to the new technology, the researchers say, is the unusual capability of carbon nanotubes. An outgrowth of nanotechnology, which deals with extraordinarily small particles near the molecular level, these nanotubes are long, hollow structures that have unique mechanical, optical and electronic properties, and are finding many applications.
In this case, carbon nanotubes can be used to detect a protein on the surface of a sensor. The nanotubes change their electrical resistance when a protein lands on them, and the extent of this change can be measured to determine the presence of a particular protein – such as serum and ductal protein biomarkers that may be indicators of breast cancer.
The newest advance was the creation of a way to keep proteins from sticking to other surfaces, like fluid sticking to the wall of a pipe. By finding a way to essentially ‘grease the pipe,’ OSU researchers were able to speed the sensing process by 2.5 times.
Further work is needed to improve the selective binding of proteins, the scientists said, before it is ready to develop into commercial biosensors.
‘Electronic detection of blood-borne biomarker proteins offers the exciting possibility of point-of-care medical diagnostics,’ the researchers wrote in their study. ‘Ideally such electronic biosensor devices would be low-cost and would quantify multiple biomarkers within a few minutes.’ Oregon State University

Children born with cleft lip, cleft palate and other craniofacial disorders face numerous medical challenges beyond appearance.
Patients can face serious airway, feeding, speech and hearing problems, as well as social and psychological challenges, Laura Swibel Rosenthal, MD, of Loyola University Medical Center and colleagues write.
‘The management of patients with craniofacial syndromes is complex,’ Rosenthal and colleagues write. ‘Otolaryngologic [ear-nose-throat] evaluation is of paramount importance in providing adequate care for this patient population.’
About 1 in 600 babies in the United States is born with a cleft lip and/or cleft palate, according to the Cleft Palate Foundation. The defect can range from a small notch in the lip to a grove that runs into the roof of the mouth. It can occur in isolation or in combination with other craniofacial birth defects. (A craniofacial disorder refers to an abnormality of the face and/or head.)
The first step in managing craniofacial patients is ensuring a safe airway. There’s also a great potential for nasal obstruction and sleep apnoea. And patients are at increased risk of developing upper airway problems such as sinusitis, laryngitis and rhinitis.
Hearing loss is common and often progressive. Thus, in addition to receiving standard newborn hearing screening, craniofacial patients should continue to receive periodic hearing tests, Rosenthal and colleagues write.
Craniofacial patients typically require several corrective surgeries, performed in staged fashion. Surgeons and anaesthesiologists should be aware of the potential challenges these patients may have with general anaesthesia.
The authors recommend a multidisciplinary approach, beginning with genetic counselling to determine the cause of the malformation, to inform parents about what to expect and to learn about the implications for other family members.
In addition to otolaryngologists, other specialists who typically care for craniofacial patients include pulmonologists, gastroenterologists, dentists and orthodontists. Depending on the congenital condition, a patient also may see pediatric specialists, such as cardiologists, ophthalmologists, neurosurgeons, endocrinologists, urologists, nephrologists and orthopaedic surgeons.
Most patients also need additional support services, including case management (social work), psychology or psychiatry, speech pathology, physical therapy, occupational therapy and other educational services. Loyola University Health System