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For the sake of this question, let's imagine a person who lives to 200, would it be at all possible for them not to get dementia? Is it an inevitable disease as we get older or can it be avoided?
Circulating miRNAs as biomarkers for neurodegenerative disorders
Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and frontotemporal dementias (FTD), are considered distinct entities, however, there is increasing evidence of an overlap from the clinical, pathological and genetic points of view. All neurodegenerative diseases are characterized by neuronal loss and death in specific areas of the brain, for example, hippocampus and cortex for AD, midbrain for PD, frontal and temporal lobes for FTD. Loss of neurons is a relatively late event in the progression of neurodegenerative diseases that is typically preceded by other events such as metabolic changes, synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities, such as axonal transport defects. The brain's ability to compensate for these dysfunctions occurs over a long period of time and results in late clinical manifestation of symptoms, when successful pharmacological intervention is no longer feasible. Currently, diagnosis of AD, PD and different forms of dementia is based primarily on analysis of the patient's cognitive function. It is therefore important to find non-invasive diagnostic methods useful to detect neurodegenerative diseases during early, preferably asymptomatic stages, when a pharmacological intervention is still possible. Altered expression of microRNAs (miRNAs) in many disease states, including neurodegeneration, and increasing relevance of miRNAs in biofluids in different pathologies has prompted the study of their possible application as neurodegenerative diseases biomarkers in order to identify new therapeutic targets. Here, we review what is known about the role of miRNAs in the pathogenesis of neurodegeneration and the possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative conditions.
Neurodegenerative diseases affect millions of people worldwide. Alzheimer&rsquos disease and Parkinson&rsquos disease are the most common neurodegenerative diseases. In 2016, an estimated 5.4 million Americans were living with Alzheimer&rsquos disease. An estimated 930,000 people in the United States could be living with Parkinson&rsquos disease by 2020.
Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, there is currently no way to slow disease progression and no known cures.
The risk of being affected by a neurodegenerative disease increases dramatically with age. More Americans living longer means more people may be affected by neurodegenerative diseases in coming decades. This situation creates a critical need to improve our understanding of what causes neurodegenerative diseases and develop new approaches for treatment and prevention.
Scientists recognize that the combination of a person&rsquos genes and environment contributes to their risk of developing a neurodegenerative disease. That is, a person might have a gene that makes them more susceptible to a certain neurodegenerative disease. But whether, when, and how severely the person is affected depends on environmental exposures throughout life.
Key research challenges are identifying and measuring exposures that may have occurred before an individual is diagnosed and disentangling the effects of these exposures.
What NIEHS is Doing
NIEHS funds research projects that look at how exposure to pesticides, pollution, and other contaminants, alone and in combination with specific genes, affects neurodegeneration.
NIEHS also provides funding for career development programs to support researchers and cultivate the next generation of leaders in the field.
Grant recipients study the following diseases:
Grant recipients study the following types of environmental factors:
- , fungicides, and insecticides
- Metals (e.g., arsenic, lead, manganese)
- Chemicals used in industry or consumer products (e.g., polychlorinated biphenyls (PCBs)
- Air pollution
- Biological factors (e.g., endotoxins produced by bacteria)
- Dietary and lifestyle factors (e.g., caffeine, tobacco smoke, dietary antioxidants)
Learn more about environmental factors that may be associated with Parkinson&rsquos Disease in the Health and Education section.
How is Dementia Diagnosed?
To diagnose dementia, doctors first assess whether a person has an underlying treatable condition such as abnormal thyroid function, normal pressure hydrocephalus, or a vitamin deficiency that may relate to cognitive difficulties. Early detection of symptoms is important, as some causes can be treated. In many cases, the specific type of dementia a person has may not be confirmed until after the person has died and the brain is examined.
A medical assessment for dementia generally includes:
- Medical history. Typical questions about a person's medical and family history might include asking about whether dementia runs in the family, how and when symptoms began, changes in behavior and personality, and if the person is taking certain medications that might cause or worsen symptoms.
- Physical exam. Measuring blood pressure and other vital signs may help physicians detect conditions that might cause or occur with dementia. Some conditions may be treatable.
- Neurological tests. Assessing balance, sensory response, reflexes, and other cognitive functions helps identify conditions that may affect the diagnosis or are treatable with drugs.
What Tests are Used to Diagnose Dementia?
The following procedures also may be used to diagnose dementia:
- Cognitive and neuropsychological tests. These tests are used to assess memory, problem solving, language skills, math skills, and other abilities related to mental functioning.
- Laboratory tests. Testing a person's blood and other fluids, as well as checking levels of various chemicals, hormones, and vitamins, can help find or rule out possible causes of symptoms.
- Brain scans. These tests can identify strokes, tumors, and other problems that can cause dementia. Scans also identify changes in the brain's structure and function. The most common scans are:
- Computed tomography (CT), which uses x rays to produce images of the brain and other organs
- Magnetic resonance imaging (MRI), which uses magnetic fields and radio waves to produce detailed images of body structures, including tissues, organs, bones, and nerves
- Positron emission tomography (PET), which uses radiation to provide pictures of brain activity
Researchers uncover link between neurodegenerative diseases and molecular scaffold
Researchers from King's College London (KCL) claim to have uncovered a link between a molecular scaffold, that allows for interaction between key components of a cell, and the debilitating effects of neurodegenerative diseases. It is possible in the long term that this line of research will yield a new target for tailored treatment in the fight against devastating afflictions such as dementia and motor neuron disease.
The team made the discovery by observing two components of a cell, the mitochondria and the endoplasmic reticulum (ER). The mitochondria is an organelle that produces the majority of the chemical energy used by the cell via the production of adenosine triphosphate. The role of the ER is to make protein and store calcium, which is needed by the cell for signalling processes. It has been discovered that many important functions within a cell are carried out via an interaction between these two cell components.
Until recently, it was not fully established as to what was responsible for the bond between the mitochondria and the ER. However the team from KCL discovered that the ER created protein VAPB binds with the mitochondrial protein known as PTPIP51 to create a molecular scaffold. This allows for a close association between the two organelles. Furthermore it was found that by increasing the concentration of the two proteins, the researchers could make the bonds grow tighter, thus proving the relationship between the proteins and the molecular scaffold.
"At the molecular level, many processes go wrong in dementia and motor neuron disease, and one of the puzzles we’re faced with is whether there is a common pathway connecting these different processes" states Professor Chris Miller, a member of the Department of Neuroscience at KCL and lead author of the paper on the team's findings. "Our study suggests that the loosening of this ‘scaffold’ between the mitochondria and ER in the cell may be a key process in neurodegenerative diseases such as dementia or motor neuron disease."
When an individual is suffering from a neurodegenerative disease, the bonds between the mitochondria and the ER are disrupted, with the result that many of the vital functions carried out via the symbiosis of the mitochondria and the ER are also undermined. With this in mind the researchers observed how the cells of a mouse were affected by the addition of TDP-43, a protein linked to both Amyotrophic Lateral Sclerosis, a form of motor neuron disease, and Fronto-Temporal Dementia, the second most common form of dementia.
It was discovered that the introduction of TDP-43 caused a significant loosening in the molecular scaffolding that binds the mitochondria and the ER, causing the disruption in cell function that comes as the inevitable product of a disease such as dementia. In light of the team's recent findings, future research may attempt to create a targeted drug to combat the breakdown of the scaffold, with the long term aim of creating new, targeted courses of treatment to combat these degenerative diseases.
The research has been published in the journal Nature Communications.
Could This Blood Test Revolutionise How Dementia and Other Neurodegenerative Diseases Are Diagnosed?
Every 3.2 seconds someone in the world is diagnosed with dementia. Approximately 46.8 million people live with dementia and it is estimated by 2050 this will more than double to 152 million people. There is currently no cure for Alzheimer's disease or any other type of dementia. Diagnosis is complicated and a series of tests are required to achieve a diagnosis. By the time these tests are taken, it’s usually because the individual has been showing clear signs of dementia and the damage is already well underway.
Today, there is no single test which accurately diagnoses Alzheimer’s. A clinical assessment to diagnose Alzheimer's is largely still a process of elimination and involves a combination of tests, from cognitive screening, neuropsychological tests, brain imaging tests, genetic tests, spinal fluid tests and PET scans for amyloid. This represents a significant hurdle not just for diagnosis, but for drug development as well. To find a cure for Alzheimer’s, researchers need to know how effective drugs are in halting, and potentially reversing, the disease. An important step towards achieving this is by identifying a toolkit of non-invasive “biomarkers” to diagnose dementia, measure disease progression and monitor the effectiveness of new therapeutic drugs.
This is what co-founders Dhivya Venkat and Dr Yamuna Krishnan are working to solve through their company, Esya Labs. Dr Krishnan is professor of chemistry and brain research foundation fellow at the Grossman Institute of Neuroscience and Quantitative Biology at the University of Chicago. She pioneered the application of DNA nanotechnology to live imaging and is the youngest woman in history to win India’s highest scientific recognition: the Bhatnagar award for Chemical Sciences.
Dr Yamuna Krishnan, co-founder of Esya Labs collecting the Infosys Prize from noble laureate Kip . [+] Thorne
Esya Labs is on a mission is to revolutionize the way neurodegenerative diseases such as dementia are currently diagnosed, building precision diagnostics using their breakthrough cell-scanning nanotechnology for early and accurate identification, well before the disease symptoms manifest physically. Their aim is that this will allow treatment to commence before the damage sets in, thereby giving the patient a better outcome.
After seven years of research and circa $8 million of research grants, Esya, headquartered out of Chicago, Illinois, has pioneered a patented technology that is a potential game-changer in this space.
How does it work?
Through a simple blood test or skin biopsy, using their patented DNA devices, Esya Labs can measure and monitor disease progression for neurocognitive diseases (e.g. Alzheimer’s), and assist pharmaceutical companies with drug development by quantifying patients’ response to a treatment. This means that they can facilitate personalized medicine by pre-assessing the best-suited treatment for individual patients.
Esya’s technology is architected using DNA filaments as building blocks to create DNA sensors. Their patented nanodevices are essentially filaments of DNA knitted together that hold measuring devices for specific chemicals.
"We use this to interrogate living cells in culture to understand how the cells function. Using our sensor technology we image key chemicals within the Lysosome, building a toolkit of non-invasive biomarkers to diagnose neurodegenerative diseases at the earliest stage," Esya Labs CEO Venkat explains.
Biomarkers are a set of chemical signatures which allow you to uniquely identify disease and they can also tell you how someone responds to a treatment for the disease. Our biomarkers measure pH and the relative levels of ions such as calcium, chloride, potassium, etc., within the organelles of cells obtained through a blood draw or skin biopsy from the patient. Just like organs of the body perform specific functions for the body, organelles of cells perform specific functions for cells. By monitoring the organelles of a cell, we can tell when they malfunction and what diseases will start manifesting as a result.”
A scientist in a laboratory places test tubes with blood or urine in the container of a thermal . [+] analyzer. Modern medical computerized equipment
Our toolkit of biomarkers profile the lysosome, an organelle which numerous studies have linked to neurocognitive impairments. With our patented technology, we hope to diagnose early onset of Alzheimer’s disease and work in partnership with therapeutic companies to facilitate drug developments and eventually personalized healthcare.”
Venkat says initial trials of Esya’s technology have been completed for lysosomal diseases and Alzheimer’s.
"Following outstanding results in our pilot, we can already see differences in patients who have manifested Alzheimer’s due to different genetic mutations. We want to expand this dataset to include a larger sample size and to be able to follow patients over time. In conjunction, we’re building partnerships with Alzheimer’s drug discovery companies for utilization of our technology to facilitate therapeutics development," Venkat adds.
Esya Labs has an ambitious time frame, hoping that in three years from now, subject to all the regulatory approvals their diagnosis biomarkers will be on the market.
Notwithstanding the growing demand for an effective drug to treat Alzheimer’s disease, it’s been nearly two decades since the last novel drug for Alzheimer’s was approved. The only way to definitely diagnose Alzheimer's disease is after death, through an autopsy of the brain tissue combined with the clinical history. The hope is that Esya’s biomarkers will disrupt a market sorely in need of precision diagnosis and drug discovery.
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Age-Associated Diseases and Cognition
A variety of factors can cause cumulative damage to the brain with age and produce cognitive impairments. These factors include damage to the brain due to cerebral ischemia, head trauma, toxins such as alcohol, excess stress hormones, or the development of a degenerative dementia such as AD. Degenerative dementias are the most common cause of significant late-life cognitive decline, but a combination of factors is common. Community-based autopsy series of patients who died with dementia found that the most common cause of dementia was AD, followed by vascular dementia, and then dementia with Lewy bodies. 26 However, mixed dementia or dementia caused by more than one pathology was very common. 27 These same pathologic changes are very common in older adults without dementia. In a large clinical-pathologic study of older adults without dementia combining participants from the Rush Memory and Aging Project and the Religious Orders Study, 100% had neurofibrillary tangles, 82% had amyloid plaques, 29% had macroscopic infarcts, 25% microscopic infarcts, and 6% had neocortical Lewy bodies. 28 Because of the very common overlap of disease-associated pathology and cognitive decline in the elderly population, it is difficult to separate disease-related declines in cognition from those due the normal aging. A recent larger study from the same longitudinal studies found that faster rates of cognitive decline were associated with AD pathology, macroscopic infarcts, and neocortical Lewy bodies, but the combination of all of these pathologies explained only 41% of the variation in rate of decline in this sample of older adults without dementia. 29 Thus, these late-life diseases cause an acceleration of cognitive decline that results in the development of dementia in many patients, but some older adults without dementia do have cognitive decline not caused by these pathologic changes.
AD is the most common cause of cognitive decline in older adults. The prevalence of clinically diagnosed AD increases exponentially with age. At age 65, less than 5% of the population has a clinical diagnosis of AD, but this number increases to more than 40% beyond age 85. 2 30 For patients who develop AD, most first demonstrate a subtle decline in memory and new learning, followed by mild changes in executive cognitive function and later changes in language and visuospatial processing. Many of these changes in cognition are similar to normal cognitive aging changes, but differ by severity. 31 32 The onset of cognitive decline is subtle and hard to determine. Progression is gradual and may be more apparent to family members than the patient. Clinically, most patients first develop mild cognitive impairment (MCI), which is defined as a syndrome of cognitive complaints, measureable mild declines in cognition, but no change in functional abilities, including instrumental activities of daily living. MCI can involve one or more cognitive domains, but memory domain-only MCI (i.e., amnestic MCI) is seen most commonly in patients who go on to develop AD. If cognitive impairments continue to progress and the patient develops evidence of functional impairment caused by these cognitive impairments, then he or she would be diagnosed as having dementia. If the patient meets the clinical criteria for AD, then he or she would be diagnosed with probable AD. Longitudinal studies suggest that the conversion rate from amnestic MCI to probable AD is % per year. 33
The development of biomarkers for AD has improved our ability to understand the temporal sequence of changes that occur in the brain of someone with AD. The development of amyloid positron emission tomography (PET) imaging (e.g., Pittsburgh Compound B/PiB) has allowed researchers to detect the presence of amyloid plaque deposition in living subjects. Studies in subjects with genetic forms of AD demonstrate that amyloid plaques can be detected 15 years before clinical symptom onset and cortical amyloid deposition is the earliest marker of AD pathology. 34 PET imaging of glucose metabolism uses fluorodeoxyglucose (FDG-PET) as a marker of neuronal activity and neurodegeneration. Glucose metabolism, as detected by FDG-PET, declines in the posterior cingulate gyrus and the association cortices of the temporal and parietal lobes closer to the time of measureable cognitive decline. Additional markers of neurodegeneration include volumetric MRI measurements of the hippocampus and measurements of cerebrospinal fluid levels of the protein tau. These biomarkers begin to show changes before very mild cognitive symptoms appear and can be measured. New diagnostic classifications for AD have recently been proposed that incorporate these biomarkers. 35 36 This classification system includes a determination of whether there is evidence of amyloid deposition, neurodegeneration, or both and whether cognition and function are normal or abnormal. Patients with stage 1 disease have cerebral amyloidosis only those with stage 2 disease have amyloidosis plus neurodegeneration but no cognitive decline those with stage 3 disease have amyloidosis, neurodegeneration, subtle cognitive decline, but no functional decline and those with stage 4 disease have amyloidosis and neurodegeneration, with measurable cognitive and functional decline. The availability of these new biomarkers and the new classification system has been helpful to define preclinical AD for prevention trials individuals with preclinical AD have evidence of amyloid deposition on amyloid PET imaging, but normal cognition and function (i.e., stage 1 and 2 AD), and AD biomarkers predict incident cognitive impairment in cognitively normal subjects followed longitudinally. 37
Recently, Jack et al examined a large cohort of subjects with normal cognition age 50 to 89 for evidence of amyloid deposition using PET imaging and evidence of neurodegeneration using MRI measurements of the hippocampus and FDG-PET measurements of hypometabolism. 38 He divided the cohort into four groups based upon biomarker results, specifically classifying amyloid imaging results into positive (A+) or negative (A−) and classifying combined neurodegeneration biomarker results into positive (N+) or negative (N−). With this classification, the A−N− group would be classified as having normal biomarkers, the A−N+ group would have suspected non-Alzheimer pathology (SNAP) with neurodegeneration, and the A+N− and A+N+ groups would have evidence of different stages of AD pathology (i.e., stage 1 and 2 AD, respectively). In this study, the population frequency of A−N− (normal biomarkers) was 100% at age 50 and declined to 17% by age 89. The frequency of A+N+ (AD with neurodegeneration) increased to 42% by age 89. The frequency of A−N+ (SNAP) increased to 24% by age 89. Thus, AD pathology with neurodegeneration and SNAP with neurodegeneration become increasingly more common with age and affected up to 66% of people by age 89, despite normal performance on cognitive testing.
The Aging Brain Needs REST
Why do neurodegenerative diseases such as Alzheimer’s affect only the elderly? Why do some people live to be over 100 with intact cognitive function while others develop dementia decades earlier?
More than a century of research into the causes of dementia has focused on the clumps and tangles of abnormal proteins that appear in the brains of people with neurodegenerative diseases. However, scientists know that at least one piece of the puzzle has been missing because some people with these abnormal protein clumps show few or no signs of cognitive decline.
A new study offers an explanation for these longstanding mysteries. Researchers have discovered that a gene regulator active during fetal brain development, called REST, switches back on later in life to protect aging neurons from various stresses, including the toxic effects of abnormal proteins. The researchers also showed that REST is lost in critical brain regions of people with Alzheimer’s and mild cognitive impairment.
“Our work raises the possibility that the abnormal protein aggregates associated with Alzheimer’s and other neurodegenerative diseases may not be sufficient to cause dementia you may also need a failure of the brain’s stress response system,” said Bruce Yankner, Harvard Medical School professor of genetics and leader of the study.
“If true, this opens up a new area in terms of treatment possibilities for the more than 5 million Americans currently living with Alzheimer’s disease,” said Yankner, who in the 1990s was the first to demonstrate the toxic effects of amyloid beta, the hallmark abnormal protein in Alzheimer’s.
The results were published Mar. 19 in Nature.
Protection at the end of life
The CDC lists Alzheimer’s disease as the sixth leading cause of death in the United States, and a Mar. 5 paper in Neurology by a group unrelated to Yankner’s argued that it should be ranked third. A 2013 study by the RAND Corporation found that with an estimated annual toll of as much as $215 billion, Alzheimer’s is America’s most expensive disease, costing more than heart disease or cancer.
“Dementia is not an inevitable result of aging,” said Yankner, who is also co-director of the Paul F. Glenn Laboratories for Biological Mechanisms of Aging. “We know it’s possible for the human brain to work normally for a century or more. So a robust mechanism must have evolved to preserve brain function and keep brain cells alive in long-lived organisms like us. We just haven’t learned what that mechanism is.”
Yankner believes REST may be a key piece in the solution to that puzzle. REST first came to his attention when team member Tao Lu, HMS instructor in genetics, flagged it as the most strongly activated transcriptional regulator—a switch that turns genes on or off—in the aging human brain. The team confirmed the finding through biochemical and molecular tests and high-resolution imaging.
The finding surprised him at first because until then, REST’s only known activity in the brain occurred prenatally, when it keeps key genes turned off until progenitor cells are ready to differentiate into functional, mature neurons. REST was believed to wind down in the brain soon after birth. (It stays active elsewhere in the body and appears to protect against several kinds of cancer and other diseases.) When Yankner thought more about it, however, it began to make sense.
“When in a person’s life are brain cells most vulnerable?” he asked. “The first time is during fetal development, when loss of young neurons would be devastating. The second is during aging, when you’re bombarded by oxidative stress and misfolded or aggregated proteins, such as the amyloid beta and tau proteins seen in Alzheimer’s disease. It makes sense that a system would come on at those two times to protect neurons, which are largely irreplaceable.”
Having discovered this possible new role for REST, Yankner and team went on to identify the specific genes REST regulates in aging neurons. They found that REST turns off genes that promote brain cell death and contribute to various pathological features of Alzheimer’s disease, such as amyloid plaques and neurofibrillary tangles, while it turns on genes that help neurons respond to stress.
Lab dish experiments revealed that removing REST made neurons more vulnerable to the toxic effects of oxidative stress and amyloid beta. REST appeared to clear away and protect against the free radicals that result from oxidative stress.
To confirm REST’s role, the team engineered mice that lacked REST only in their brains and watched what happened as they aged.
“The mice were okay as young adults, but as they got older, neurons in the brain started to die in the same places as in Alzheimer’s: the hippocampus and the cortex,” said Yankner. “This suggested that REST is essential for neurons to remain alive in the aging brain.”
Together with HMS associate professor of genetics Monica Colaiácovo, the team also uncovered a REST equivalent in the tiny worm C. elegans. There, too, the REST equivalent was necessary to protect against free radicals and amyloid toxicity. This suggested the protective function is shared across species.
Diverted from its course
Yankner and colleagues further illuminated the relationship between REST and the aging brain through a combination of lab experiments and studies of brain tissue from elderly people with and without dementia.
The team showed that REST was activated in normal aging brains. The brains of people who developed mild cognitive impairment, by contrast, showed an early decline in REST. The affected brain regions of people with Alzheimer’s had hardly any REST left.
“REST loss correlates very closely with memory loss, especially episodic or autobiographical memory, the type that typically declines early in Alzheimer’s,” said Yankner.
Cell culture experiments suggested REST is activated when stressed neurons send signals to one another, and that once REST is created in a neuron’s cytoplasm, it must travel to the nucleus to do its job.
Yankner’s group then found that in Alzheimer’s, REST gets diverted from its journey to the nucleus, becomes engulfed through a process called autophagy and is eventually destroyed.
The team saw the same striking misplacement of REST when they looked at brain tissue from people with other prevalent neurodegenerative diseases involving dementia, including frontotemporal dementia and dementia with Lewy bodies. In all three dementing illnesses, REST had been swept into the cellular trash bins alongside each disease’s abnormal proteins: amyloid beta in Alzheimer’s, tau in frontotemporal dementia and alpha-synuclein in Lewy body disease.
“The prevention of REST from getting to the nucleus may be the earliest phase in the loss of REST function. Our laboratory models suggest that this will make neurons much more vulnerable to a variety of stresses and toxic proteins,” said Yankner.
Uncovering how REST gets activated and misplaced provides new ideas for how to intercept Alzheimer’s. For instance, rather than solely focusing on lowering amyloid beta levels, as clinical trials have done so far without great success, Yankner imagines trying to target REST with drugs such as lithium, which his lab has shown can boost REST function.
REST and dementia-free longevity
Next, Yankner turned to the long-standing puzzle in neurology of how some aging individuals can harbor Alzheimer’s disease pathological changes but never become demented.
The team examined brain tissue gathered as part of the Religious Orders Study and the Rush Memory and Aging Project, both funded by the National Institute on Aging. These long-term studies together follow several thousand aging participants and collect donated tissue after death to better understand normal aging, cognitive impairment and neurodegenerative disease.
The team sorted the samples into two groups. One group had Alzheimer’s pathology and experienced symptoms of dementia. The second group had the same amount of Alzheimer’s pathology but did not become demented. The team found that the group with no dementia had at least three times more REST in the nuclei of their neurons in key brain regions.
“This suggests a person may be able to resist the toxic effects of Alzheimer’s pathology if REST levels remain high,” said Yankner. “If we could activate this stress-resistance gene network with drugs, it might be possible to intervene in the disease quite early.”
“Since Alzheimer’s strikes late in life, delaying the onset of disease by just a few years could have a very substantial impact,” he added.
In additional studies, the team found that REST strongly correlated with increased longevity. REST levels were highest in the brains of people who lived into their 90s and 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer’s, suggesting that they might be protected from dementia.
Finally, the team showed that REST increases the expression of several genes known to increase lifespan in model systems of aging.
It remains to be seen how many more pieces will slot in alongside REST in solving the puzzle of aging and dementia. For now, the team’s findings offer new ideas for combating a disease that currently has no treatment.
“I’m sure there is something else at play that hasn’t been seen or measured yet. REST won’t be the end-all. But I think our work will help shift attention to this protective pathway in the aging brain and its role in the prevention of Alzheimer’s and other dementing diseases,” said Yankner.
“It’s a new point of view on the problem.”
This study was supported by the National Institutes of Health (Director’s Pioneer Award DP1OD006849 and grants P01AG27916, R01AG26651, R01GM072551, P30AG10161, R01AG15819 and R01AG17917) and the Glenn Foundation for Medical Research.