Posts tagged neurodegenerative diseases
Articles and news from the latest research reports.
Chipmaker Races to Save Stephen Hawking’s Speech as His Condition Deteriorates
Intel is developing communication technology that can quickly process and respond to signals Hawking sends from the few muscles in his body that he can still control
(Image: Wikimedia Commons)
Researchers turn one form of neuron into another in the brain
A new finding by Harvard stem cell biologists turns one of the basics of neurobiology on its head – demonstrating that it is possible to turn one type of already differentiated neuron into another within the brain.
The discovery by Paola Arlotta and Caroline Rouaux “tells you that maybe the brain is not as immutable as we always thought, because at least during an early window of time one can reprogram the identity of one neuronal class into another,” said Arlotta, an Associate Professor in Harvard’s Department of Stem Cell and Regenerative Biology (SCRB).
The principle of direct lineage reprogramming of differentiated cells within the body was first proven by SCRB co-chair and Harvard Stem Cell Institute (HSCI) co-director Doug Melton and colleagues five years ago, when they reprogrammed exocrine pancreatic cells directly into insulin producing beta cells.
Arlotta and Rouaux now have proven that neurons too can change their mind. The work is being published on-line by the journal Nature Cell Biology.
In their experiments, Arlotta targeted callosal projection neurons, which connect the two hemispheres of the brain, and turned them into neurons similar to corticospinal motor neurons, one of two populations of neurons destroyed in Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease. To achieve such reprogramming of neuronal identity, the researchers used a transcription factor called Fezf2, which long as been known for playing a central role in the development of corticospinal neurons in the embryo.
What makes the finding even more significant is that the work was done in the brains of living mice, rather than in collections of cells in laboratory dishes. The mice were young, so researchers still do not know if neuronal reprogramming will be possible in older laboratory animals – and humans. If it is possible, this has enormous implications for the treatment of neurodegenerative diseases.
"Neurodegenerative diseases typically effect a specific population of neurons, leaving many others untouched. For example, in ALS it is corticospinal motor neurons in the brain and motor neurons in the spinal cord, among the many neurons of the nervous system, that selectively die," Arlotta said. "What if one could take neurons that are spared in a given disease and turn them directly into the neurons that die off? In ALS, if you could generate even a small percentage of corticospinal motor neurons, it would likely be sufficient to recover basic functioning," she said.
The experiments that led to the new finding began five years ago, when “we wondered: in nature you never seen a neuron change identity; are we just not seeing it, or is this the reality? Can we take one type of neuron and turn it into another?” Arlotta and Rouaux asked themselves.
Over the course of the five years, the researchers analyzed “thousands and thousands of neurons, looking for many molecular markers as well as new connectivity that would indicate that reprogramming was occurring,” Arlotta said. “We could have had this two years ago, but while this was a conceptually very simple set of experiments, it was technically difficult. The work was meant to test important dogmas on the irreversible nature of neurons in vivo. We had to prove, without a shadow of a doubt, that this was happening.”
The work in Arlotta’s lab is focused on the cerebral cortex, but “it opens the door to reprogramming in other areas of the central nervous system,” she said.
Arlotta, an HSCI principal faculty member, is now working with colleague Takao Hensch, of Harvard’s Department of Molecular and Cellular Biology, to explicate the physiology of the reprogrammed neurons, and learn how they communicate within pre-existing neuronal networks.
"My hope is that this will facilitate work in a new field of neurobiology that explores the boundaries and power of neuronal reprogramming to re-engineer circuits relevant to disease," said Paola Arlotta.
(Image courtesy Tulane University)
Blood-Based Biomarkers May Lead to Earlier Diagnosis of Parkinson’s Disease
Pilot Study Published in the Journal of Parkinson’s Disease
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"The ideal biomarker should be minimally-invasive, cost efficient, quantifiable, reproducible, specific, and sensitive," explains lead investigator Sok Kean Khoo, PhD, of the Center for Neurodegenerative Science and Genomic Microarray Core Facility at the Van Andel Institute, Grand Rapids, Michigan. "Biofluids such as plasma could provide an ideal resource for development of such desirable biomarkers. However, clinical diagnostic tests based on biochemical analysis of biofluids from PD patients have yet to be established," she continues.
Investigators hypothesized that specific miRNAs related to PD can be detected in plasma. It is known that miRNAs detected in various cells and tissues can also be found in biofluids such as blood plasma and serum. A preliminary study using miRNA microarrays showed that approximately 4% (35/866) of miRNAs from healthy brain tissues could also be detected in the plasma of healthy controls.
In an initial study they obtained the global miRNA expressions in plasma of an initial discovery set of 32 PD patients and 32 normal controls and identified nine pairs of PD-predictive classifiers and 13 most-differentially expressed miRNAs as potential biomarkers to discriminate PD patients from normal controls. They then used a quantitative real-time Polymerase Chain Reaction technique (qRT-PCR) to validate and evaluate the performance of these biomarkers in a new replication set of 42 PD patients and 30 controls from the same clinical site.
They then identified a combination of biomarkers that achieved the highest predictive performance and applied this panel of biomarkers to a new, independent validation set of samples from 30 PD patients from a different clinical site, which showed lower biomarker performance.
The investigators acknowledge that there are still challenges to be overcome in validating biomarker candidates due to clinical and sample variability and factors that influence miRNA expression such as comorbidities and other medication the patient is taking. However, explains Dr Khoo, “This is a proof-of-concept study to demonstrate the feasibility of using plasma-based circulating miRNAs, and the hypothesis that miRNA expression changes are associated with the neurodegenerative disease process, either directly or as part of positive feedback loops, is emerging rapidly. This study opens new opportunities to the exploration of circulating miRNAs for diagnostic, prognostic, and therapeutic interventions for PD and possibly other neurodegenerative diseases.”
"A diagnostic test to determine the status of a patient’s disease onset would provide crucial data for more timely, efficient, and successful therapeutic interventions," said Patrik Brundin, MD, PhD, Director of Van Andel Institute’s Center for Neurodegenerative Science. "There is an urgent need to develop objective, measureable biomarkers to improve PD diagnostics and help define its subtypes, and Dr. Khoo’s interesting study is an important step in that direction."
(Image: Wikipedia)
Scientists Discover Structure of Protein Essential for Quality Control, Nerve Function
Using an innovative approach, scientists at The Scripps Research Institute (TSRI) have determined the structure of Ltn1, a recently discovered “quality-control” protein that is found in the cells of all plants, fungi and animals.
Ltn1 appears to be essential for keeping cells’ protein-making machinery working smoothly. It may also be relevant to human neurodegenerative diseases, for an Ltn1 mutation in mice leads to a motor-neuron disease resembling amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease).
“To better understand Ltn1’s mechanism of action, we needed to solve its structure, and that’s what we’ve done here,” said TSRI Associate Professor Claudio Joazeiro.
“In addition, this project has brought us a set of structural analysis techniques that we can apply to other exciting problems in biology,” said TSRI Professor Bridget Carragher.
Joazeiro and Carragher, along with Clint Potter, also a TSRI professor, are senior authors of the new report, which appears in the online Early Edition of the Proceedings of the National Academy of Sciences the week of January 14, 2013.
Links to Neurodegenerative Disease
Ltn1 first turned up on biologists’ radar screens several years ago when a joint Novartis-Phenomix research team noted that mice with an unknown gene mutation were born normal but suffered from progressive paralysis. The scientists dubbed the animals lister mice, because they listed to one side as they walked. Collaborating with Joazeiro, the Novartis team reported in a 2009 paper that the mutated gene normally codes for a type of enzyme known as an E3 ubiquitin ligase, and that the mouse phenotype was due to a neurodegenerative syndrome resembling ALS.
In a study published in the journal Nature the following year, Joazeiro and his postdoctoral research associate Mario H. Bengtson found that the enzyme serves as a crucial quality-control manager for the cellular protein-making factories called ribosomes. Occasionally a ribosome receives miscoded genetic instructions and produces certain types of abnormal proteins, known as “nonstop proteins”— jamming the ribosomal machinery like a wrinkled sheet of paper in an office printer. Bengtson and Joazeiro found that Ltn1 fixes jammed ribosomes by tagging nonstop proteins with ubiquitin molecules, thereby marking them for quick destruction by roving cellular garbage-disposers called proteasomes.
“The question for us then was, ‘How does Ltn1 do this?’” said Joazeiro.
Pushing the Boundaries of Electron Microscopy
To help find out, he began a collaboration with Carragher and Potter, who run the National Resource for Automated Molecular Microscopy (NRAMM), an advanced electron microscope facility at TSRI that is funded by the National Institutes of Health’s National Center for Research Resources.
Ltn1 was deemed too large for its structure to be determined by current nuclear magnetic resonance (NMR) technology, and, as the scientists know now, too flexible to allow the highly regular crystalline packing needed by X-ray crystallographers. “It’s a very floppy molecule, so it would be hard to crystallize,” said Potter.
Advanced electron microscopy offered a way, however. Dmitry Lyumkis, a graduate student in the NRAMM laboratory and first author of the study, took high-resolution images of yeast Ltn1 with an electron microscope. He then used sophisticated image and data processing software to align and average individual images. The technique eliminates much of the random “noise” that obscures single images and produces a sharp 3D picture of the protein.
No one has ever used electron microscopy to distinguish so many—more than 20—conformations of such a small protein. “Usually electron microscopists determine no more than two or three conformational states, and they work with protein complexes whose size is in the megadalton range, but Ltn1 is only 180 kilodaltons, an order of magnitude smaller,” Lyumkis said.
An Unusually Flexible Structure
The analysis revealed that Ltn1 has an elongated, double-jointed and extraordinarily flexible structure with two working ends—the N-terminus and C-terminus. “We anticipate that the N-terminus is responsible for association with the ribosome and know that the C-terminus is responsible for the ubiquitylation of nonstop proteins,” said Lyumkis. “We suspect that the high flexibility of this structure is needed for it to work on the variety of nonstop proteins that can get stuck in ribosomes.”
One of the next steps for the team is to evaluate Ltn1’s individual segments, which appear to be more rigid, using X-ray crystallography, in order to develop a piece-by-piece atomic-resolution model of the enzyme. Another is to determine the structure of Ltn1 when it is attached to a ribosome and operating on a nonstop protein. Joazeiro notes that a typical yeast cell has nearly 200,000 ribosomes but requires only 200 Ltn1 copies for adequate quality control under normal growth conditions. “Somehow this enzyme can efficiently sense which ribosomes are jammed, and we expect that by solving the joint structure of Ltn1 and a ribosome, we’ll be able to understand how it does this,” he says.
Lyumkis, Carragher, Potter and their colleagues at NRAMM also plan to use a similar electron microscopy-based approach to find the structures of other important proteins with highly variable “heterogeneous” conformations. “Heterogeneity has been a big challenge,” said Potter, “and being able to collect this large dataset and do all of this data processing successfully has been a critical breakthrough.”
Protein identified that can disrupt embryonic brain development and neuron migration
Interneurons – nerve cells that function as ‘dimmers’ – play an important role in the brain. Their formation and migration to the cerebral cortex during the embryonic stage of development is crucial to normal brain functioning. Abnormal interneuron development and migration can eventually lead to a range of disorders and diseases, from epilepsy to Alzheimer’s. New research by Dr. Eve Seuntjens and Dr. Veronique van den Berghe of the Department of Development and Regeneration (Danny Huylebroeck laboratory, Faculty of Medicine) has identified two proteins, Sip1 and Unc5b, that play an important role in the development and migration of interneurons to the cerebral cortex – a breakthrough in our understanding of early brain development.
Two types of nerve cells are crucial to healthy brain functioning. Projection neurons, the more widely known of the two, make connections between different areas of the brain. Interneurons, a second type, work as dimmers that regulate the signalling processes of projection neurons. A shortage or irregular functioning of interneurons can cause short circuits in the nervous system. This can lead to seizures, a common symptom of many brain disorders. Interneuron dysfunction even appears to play a role in schizophrenia, autism and neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS.
Trailblazers
Researchers have only recently understood how different kinds of neuron are formed during embryonic development. During early brain development, stem cells form projection neurons in the cerebral cortex. Interneurons are made elsewhere in the brain. These interneurons then migrate to the cortex to mix with the projection neurons. Dr. Eve Seuntjens of the Celgen laboratory led by Professor Danny Huylebroeck explains: “The journey of interneurons is very complex: their environment changes constantly during growth and there are no existing structures — such as nerve pathways — available for them to follow.”
The question is how young interneurons receive their ‘directions’ to the cerebral cortex. Several proteins play a role, says Dr. Seuntjens. “We changed the gene containing the production code for the protein Sip1 in mice so that this protein was no longer produced during brain development. In those mice, the interneurons never made it to the cerebral cortex — they couldn’t find the way.
That has to do with the guidance signals – substances that repel or attract interneurons and thus point them in the right direction – encountered by the interneurons on their way to the cerebral cortex. Without Sip1 production, interneurons see things through an overly sharp lens, so to speak. They see too many stop signs and become blocked. That overly sharp lens is Unc5b, a protein. Unc5b is deactivated by Sip1 in healthy mice. There are several known factors that influence the migration of interneurons, but Unc5b is the first protein we’ve isolated that we now know must be switched off in order for interneuron migration to move ahead smoothly.”
The next step is to study this process in the neurons of humans. “Now that there are techniques to create stem cells from skin cells, we can mimic the development of stem cells into interneurons and study what can go wrong. From there, we can test whether certain drugs can reverse the damage. That’s all still on the horizon, but you can see that the focus of research on many brain disorders and diseases is increasingly shifting to early child development because that just might be where a cause can be found.”
Potential Drug Target to Block Cell Death in Parkinson’s Disease
Oxidative stress is a primary villain in a host of diseases that range from cancer and heart failure to Alzheimer’s disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease. Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have found that blocking the interaction of a critical enzyme may counteract the destruction of neurons associated with these neurodegenerative diseases, suggesting a potential new target for drug development.
These findings appear in the January 11, 2013 edition of The Journal of Biological Chemistry.
During periods of cellular stress, such as exposure to UV radiation, the number of highly reactive oxygen-containing molecules can increase in cells, resulting in serious damage. However, relatively little is known about the role played in this process by a number of stress-related enzymes.
In the new study, the TSRI team led by Professor Philip LoGrasso focused on an enzyme known as c-jun-N-terminal kinase (JNK). Under stress, JNK migrates to the mitochondria, the part of the cell that generates chemical energy and is involved in cell growth and death. That migration, coupled with JNK activation, is associated with a number of serious health issues, including mitochondrial dysfunction, which has long been known to contribute to neuronal death in Parkinson’s disease.
The new study showed for the first time that the interaction of JNK with a protein known as Sab is responsible for the initial JNK localization to the mitochondria in neurons. The scientists also found blocking JNK mitochondrial signaling by inhibiting JNK interaction with Sab can protect against neuronal damage in both cell culture and in the brain.
In addition, by treating JNK with a peptide inhibitor derived from a mitochondrial membrane protein, the team was able to induce a two-fold level of protection of neurons in the substantia nigra pars compacta, the brain region devastated by Parkinson’s disease.
The study noted that this inhibition leaves all other cell signaling intact, which could mean potentially fewer side effects in any future therapies.
“This may be a novel way to prevent neuron degeneration,” said LoGrasso. “Now we can try to make compounds that block that translocation and see if they’re therapeutically viable.”
USF and VA researchers find long-term consequences for those suffering traumatic brain injury
Researchers from the University of South Florida and colleagues at the James A. Haley Veterans’ Hospital studying the long-term consequences of traumatic brain injury (TBI) using rat models, have found that, overtime, TBI results in progressive brain deterioration characterized by elevated inflammation and suppressed cell regeneration. However, therapeutic intervention, even in the chronic stage of TBI, may still help prevent cell death.
Their study is published in the current issue of the journal PLOS ONE.
“In the U.S., an estimated 1.7 million people suffer from traumatic brain injury,” said Dr. Cesar V. Borlongan, professor and vice chair of the department of Neurosurgery and Brain Repair at the University of South Florida (USF). “In addition, TBI is responsible for 52,000 early deaths, accounts for 30 percent of all injury-related deaths, and costs approximately $52 billion yearly to treat.”
While TBI is generally considered an acute injury, secondary cell death caused by neuroinflammation and an impaired repair mechanism accompany the injury over time, said the authors. Long-term neurological deficits from TBI related to inflammation may cause more severe secondary injuries and predispose long-term survivors to age-related neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and post-traumatic dementia.
Since the U.S. military has been involved in conflicts in Iraq and Afghanistan, the incidence of traumatic brain injury suffered by troops has increased dramatically, primarily from improvised explosive devices (IEDs), according to Martin Steele, Lieutenant General, U.S. Marine Corps (retired), USF associate vice president for veterans research, and executive director of Military Partnerships. In response, the U.S. Veterans Administration has increasingly focused on TBI research and treatment.
“Progressive injury to hippocampal, cortical and thalamic regions contributes to long-term cognitive damage post-TBI,” said study co-author Dr. Paul R. Sanberg, USF senior vice president for research and innovation. “Both military and civilian patients have shown functional and cognitive deficits resulting from TBI.”
Because TBI involves both acute and chronic stages, the researchers noted that animal model research on the chronic stages of TBI could provide insight into identifying therapeutic targets for treatment in the post-acute stage.
“Using animal models of TBI, our study investigated the prolonged pathological outcomes of TBI in different parts of the brain, such as the dorsal striatum, thalamus, corpus callosum white matter, hippocampus and cerebral peduncle,” explained Borlongan, the study’s lead author. “We found that a massive neuroinflammation after TBI causes a second wave of cell death that impairs cell proliferation and impedes the brain’s regenerative capabilities.”
Upon examining the rat brains eight weeks post-trauma, the researchers found “a significant up-regulation of activated microglia cells, not only in the area of direct trauma, but also in adjacent as well as distant areas.” The location of inflammation correlated with the cell loss and impaired cell proliferation researchers observed.
Microglia cells act as the first and main form of immune defense in the central nervous system and make up 20 percent of the total glial cell population within the brain. They are distributed across large regions throughout the brain and spinal cord.
“Our study found that cell proliferation was significantly affected by a cascade of neuroinflammatory events in chronic TBI and we identified the susceptibility of newly formed cells within neurologic niches and suppression of neurological repair,” wrote the authors.
The researchers concluded that, while the progressive deterioration of the TBI-affected brain over time suppressed efforts of repair, intervention, even in the chronic stage of TBI injury, could help further deterioration.
Pioneering Research on Type 2 Diabetes
While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others.
Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.
The current work is based on a previous major finding by UCSB’s Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.
"By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells," said Marth. UCSB is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.
The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.
Dopamine-receptor gene variant linked to human longevity
A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life, UC Irvine and other researchers have found.
This derivative of a dopamine-receptor gene – called the DRD4 7R allele – appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.
Robert Moyzis, professor of biological chemistry at UC Irvine, and Dr. Nora Volkow, a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led a research effort that included data from the UC Irvine-led 90+ Study in Laguna Woods, Calif. Results appear online in The Journal of Neuroscience.
The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals’ reactivity to their environment.
People who carry this variant gene, Moyzis said, seem to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors.
“While the genetic variant may not directly influence longevity,” Moyzis said, “it is associated with personality traits that have been shown to be important for living a longer, healthier life. It’s been well documented that the more you’re involved with social and physical activities, the more likely you’ll live longer. It could be as simple as that.”
Numerous studies – including a number from the 90+ Study – have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases, such as Alzheimer’s.
Prior molecular evolutionary research led by Moyzis and Chuansheng Chen, UC Irvine professor of psychology & social behavior, indicated that this “longevity allele” was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago.
In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This “oldest-old” population had a 66 percent increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity.
Next, Volkow, neuroscientist Panayotis Thanos and their colleagues at the Brookhaven National Laboratory found that mice without the variant had a 7 percent to 9.7 percent decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment.
While it’s evident that the variant can contribute to longevity, Moyzis said further studies must take place to identify any immediate clinical benefits from the research. “However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity,” he added.
When trying to determine the root cause of a person’s dementia, using an MRI can effectively and non-invasively screen patients for Alzheimer’s disease or Frontotemporal Lobar Degeneration (FTLD), according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. Using an MRI-based algorithm effectively differentiated cases 75 percent of the time, according to the study, published in the December 26th, 2012, issue of Neurology, the medical journal of the American Academy of Neurology. The non-invasive approach reported in this study can track disease progression over time more easily and cost-effectively than other tests, particularly in clinical trials testing new therapies.
Researchers used the MRIs to predict the ratio of two biomarkers for the diseases - the proteins total tau and beta-amyloid - in the cerebrospinal fluid. Cerebrospinal fluid analyses remain the most accurate method for predicting the disease cause, but requires a more invasive lumbar puncture. “Using this novel method, we obtain a single biologically meaningful value from analyzing MRI data in this manner and then we can derive a probabilistic estimate of the likelihood of Alzheimer’s or FTLD,” said the study’s lead author, Corey McMillan, PhD, of the Perelman School of Medicine and Frontotemporal Degeneration Center at the University of Pennsylvania.
Using the MRI prediction method was 75 percent accurate at identifying the correct diagnosis in both patients with pre-confirmed disease diagnoses and those with biomarker levels confirmed by lumbar punctures, which shows comparable overlap between accuracy of the MRI and lumbar puncture methods. “For those remaining 25 percent of cases that are borderline, a lumbar puncture testing spinal fluid may provide a more accurate estimate of the pathological diagnosis.”
Accurate tests to measure disease progression are very important in neurodegenerative diseases, especially as clinical trials test new therapies to slow or stop the progression or the disease. Biomarkers for neurodegenerative diseases have been steadily improving, with new developments including spinal fluid tests detecting tau and amyloid-beta protein levels and other neuroimaging techniques developed at Penn Medicine, as part of the Alzheimer’s Disease Neuroimaging Initiative. While a spinal fluid test can be used to accurately pinpoint whether disease-specific proteins are present, the test requires a more invasive lumbar puncture making it more difficult to repeat over time. And for studies using other imaging techniques, such as test measuring whole brain volume, reduced sensitivity of the measurement requires more patients to be enrolled in clinical trials for statistical power to be achieved.
“Since this method yields a single biological value, it is possible to use MRI to screen patients for inclusion in clinical trials in a cost-effective manner and to provide an outcome measure that optimizes power in drug treatment trials,” the authors concluded.