Breaking News
September 19, 2018 - FDA-approved ‘safe’ daily BPA exposure may contribute to insulin resistance
September 19, 2018 - Research finds physical connection between the brain’s fluid reservoirs and meningeal lymphatics
September 19, 2018 - Biomedical review finds failure rates in some surgical mesh treatments to be unacceptably high
September 19, 2018 - Researchers develop more accurate measure of body fat
September 19, 2018 - Doctors and students rally to support gun violence research, education
September 19, 2018 - LEO Pharma and MorphoSys announce expansion of strategic alliance to develop peptide-derived drugs
September 19, 2018 - Seniors in pain hop aboard the canna-bus
September 19, 2018 - New compound could prevent malaria parasites from maturing inside mosquito
September 19, 2018 - Scientists find alterations in blood flow in response to body position change
September 19, 2018 - UNC Health Care extends free access to virtual care service in the aftermath of Hurricane Florence
September 19, 2018 - Opioid Refills Rare After Rhinoplasty
September 19, 2018 - Corn, obesity, and navigating healthy eating choices as a parent
September 19, 2018 - Journal editor aims to prompt thoughtful review of ethics in precision health
September 19, 2018 - Researchers identify key step in how plant cells respond to pathogens
September 18, 2018 - Researchers analyze how exposure to silver nanoparticles affects zebrafish
September 18, 2018 - Study shows air pollution may be bad for the fetus
September 18, 2018 - Coffee May Have Another Perk for Kidney Patients
September 18, 2018 - Tongue-in-cheek Nobels honor nutritional analysis of cannibalism, roller-coaster kidney stones treatment
September 18, 2018 - Progress, priorities, challenges are focus of State of Stanford Medicine | News Center
September 18, 2018 - Established Alzheimer’s Risk Gene Has a New Role
September 18, 2018 - Hospitalization after antibiotic initiation found to be higher for people with Alzheimer’s disease
September 18, 2018 - Many children with special healthcare needs do not have access to ‘PCMH-concordant’ care
September 18, 2018 - Investigational nasal influenza vaccine tested in children and teens
September 18, 2018 - Lymphatic vessels surrounding the brain play crucial role in multiple sclerosis, research suggests
September 18, 2018 - New fiber laser-based ultrasound sensor may have potential applications in medical diagnostics
September 18, 2018 - Protect your heart and health during ‘dog days’ of summer
September 18, 2018 - Faculty receive awards for promise in biomedical research, clinical care | News Center
September 18, 2018 - Digital games for CVD-related self-management improve exercise capacity and energy expenditure
September 18, 2018 - Aluminum inclusions help enhance adsorption of chemo drugs onto active carbon delivery capsule
September 18, 2018 - Adding PET scans to CT imaging can change treatment for women with cervical cancer
September 18, 2018 - UCSF awarded $20 million grant to study impacts of new, emerging tobacco products
September 18, 2018 - Human brains may be wired to prefer lying on the couch, suggests research
September 18, 2018 - Zika virus vaccine shows promise for treatment of fatal glioblastoma
September 18, 2018 - Theravance Biopharma and Mylan to Report New Data from Phase 3 Studies of Yupelri (revefenacin) in Oral Presentation at European Respiratory Society International Congress 2018
September 18, 2018 - INSiGHT identifies unique retinal regulatory genes
September 18, 2018 - Diversity, science leadership grants awarded to student-faculty pairs | News Center
September 18, 2018 - Many parents blame electronics for sleep problems among teens
September 18, 2018 - Researchers study neuronal activity in brain that prevents individuals from doing physical activity
September 18, 2018 - Purifying Proteins from Mammalian Cell Culture
September 18, 2018 - Researchers map 3D structure of toxic proteins used by Pseudomonas aeruginosa to trigger infection
September 18, 2018 - Outcome of ACL reconstruction related to the way you move post-surgery
September 18, 2018 - Study aims to investigate risk factors for PPCs in surgical patients with gastric cancer
September 18, 2018 - Ardelyx Submits New Drug Application for Tenapanor for IBS-C
September 18, 2018 - Sociodemographic disparities in eyeglass use among elderly
September 18, 2018 - New Drug Shows Promise for Progressive Form of MS
September 18, 2018 - Babies exposed to higher levels of organochlorine compounds in womb may have worse lung function
September 18, 2018 - Women exposed to trauma in their lives gave birth to underweight male infants
September 18, 2018 - Probiotic supplementation may reduce use of antibiotics, scientific analysis shows
September 18, 2018 - Resveratrol decreases pain severity and levels of inflammatory biomarkers in osteoarthritis patients
September 18, 2018 - Research shows pollution is reaching the placenta
September 18, 2018 - KAIST researchers develop heart-targeting drug delivery technology using tannin acid
September 18, 2018 - Muscle relaxants used during general anesthesia can increase risk of pulmonary complications
September 18, 2018 - Silicone breast implants may increase risk of rare adverse outcomes in women
September 18, 2018 - Pediatricians Have a Role in Encouraging Play Among Children
September 18, 2018 - California’s Medicaid program hits ‘print’ when the feds need info
September 18, 2018 - Genes, environment and schizophrenia—new study finds the placenta is the missing link
September 18, 2018 - Boehringer Ingelheim announces study results of COPD patients treated with Spiolto Respimat
September 18, 2018 - PAREXEL launches Patient Innovation Center to improve drug development process
September 18, 2018 - Children’s National and NIAID launch pediatric clinical research partnership
September 18, 2018 - Researchers may be overlooking complexities in social relations of primates
September 18, 2018 - Key signaling molecule that helps stem cells make healthy bone declines as we age
September 18, 2018 - More women veterans with chronic pain use CIH therapies than men
September 18, 2018 - As Earth Warms, Heat-Related Deaths Will Multiply
September 18, 2018 - Labetalol use up for patients with preeclampsia and asthma
September 18, 2018 - MoreGrasp project shows significant results in field of thought-controlled grasp neuroprosthetics
September 18, 2018 - Drumming can benefit school children with autism
September 18, 2018 - Busyness can help people to make virtuous choices, research shows
September 18, 2018 - Two-minute bursts of in-class exercise breaks do not disrupt learning and teaching
September 18, 2018 - New online tools aid surgeons and specialists who care for older people
September 18, 2018 - Researchers use CRISPR to identify gene that helps cells resist flavivirus infection
September 18, 2018 - Brain’s support cells may play a central role in repetitive behaviors related to OCD
September 18, 2018 - Scientists discover novel mechanism by which synthesized proteins reach target compartment in cell
September 18, 2018 - Easy and rapid test for viral infections can cut antibiotic use, hospitalizations
September 18, 2018 - Gunshot victims more likely to require blood transfusions and die than other trauma patients
September 18, 2018 - Cyclacel Pharmaceuticals Announces Initiation of Phase 1b/2 Clinical Trial of Sapacitabine With Olaparib in BRCA Mutant Breast Cancer
September 18, 2018 - Older adults fitted with cochlear implants exhibit poor brain function
September 18, 2018 - Inexpensive testing spurs cancer patients’ relatives to assess own disease risk | News Center
September 18, 2018 - Aging may have originated at the very beginning of life, says study
September 18, 2018 - New research on sperm quality updates advice for couples trying to conceive
September 18, 2018 - Paracetamol use in infancy may increase risk of developing asthma by the age of 18
The brain’s immune system may be key to new Alzheimer’s treatments

The brain’s immune system may be key to new Alzheimer’s treatments

image_pdfDownload PDFimage_print
Huaxi Xu, Ph.D., professor and director of SBP’s Neuroscience Initiative. Credit: Sanford Burnham Prebys Medical Discovery Institute

Sanford Burnham Prebys Medical Research Institute (SBP) researchers have published two new studies in Neuron that describe how TREM2, a receptor found on immune cells in the brain, interacts with toxic amyloid beta proteins to restore neurological function. The research, performed on mouse models of Alzheimer’s disease, suggests boosting TREM2 levels in the brain may prevent or reduce the severity of neurodegenerative disorders including Alzheimer’s disease.

“Our first paper identifies how amyloid beta binds to TREM2, which activates neural immune cells called microglia to degrade amyloid beta, possibly slowing Alzheimer’s disease pathogenesis,” says Huaxi Xu, Ph.D., professor and director of SBP’s Neuroscience Initiative, Jeanne and Gary Herberger Leadership Chair in Neuroscience Research and senior author of the study. “The second study shows that increasing TREM2 levels renders microglia more responsive and reduces Alzheimer’s disease symptoms.”

Alzheimer’s disease affects more than 47 million people worldwide, a number expected to grow as the population ages. One of the hallmarks of the disease is the accumulation of amyloid plaques that form between neurons and interfere with brain function. Many drug companies have been working for years to reduce amyloid beta production to thwart Alzheimer’s—but with minimal success.

“TREM2 offers a potential new strategy,” says Xu.”Researchers have known that mutations in TREM2 significantly increase Alzheimer’s risk, indicating a fundamental role for this particular receptor in protecting the brain. This new research reveals specific details about how TREM2 works, and supports future therapeutic strategies to strengthen the link between amyloid beta and TREM2, as well as increasing TREM2 levels in the brain to protect against pathological features of the disease.

Xu led the first study (TREM2 is a receptor for β-amyloid which mediates microglial function), showing that TREM2 binds quite specifically to amyloid beta. In particular, it connects with amyloid beta oligomers (proteins that bind together to form a polymer), which are the protein’s most toxic configuration. Without TREM2, microglia were much less successful at binding to, and clearing out, amyloid beta.

Further investigation showed that removing TREM2 downregulated microglial potassium ion channels, impairing the electrical currents associated with the activation of these immune cells. In addition, TREM2 turned on a number of mechanisms associated with the amyloid beta response in microglia.

The second study (TREM2 Gene Dosage Increase Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models), a collaboration led by with X. William Yang, M.D., Ph.D., professor in Jane and Terry Semel Institute for Neuroscience and Human Behavior, and Department of Psychiatry & Biobehavioral Sciences at David Geffen School of Medicine at UCLA, added TREM2 to a mouse model with aggressive Alzheimer’s disease. They found that the added TREM2 signaling stopped disease progression and even restored cognitive function.

“These studies are important because they show that in addition to rescuing the pathology associated with Alzheimer’s disease, we are able to reduce the behavioral deficits with TREM2,” says Xu. “To our knowledge this provides convincing evidence that minimizing amyloid beta levels alleviates Alzheimer’s disease symptoms.” As they learn more about how TREM2 modulates the amyloid signals that put microglia to work, the Xu lab and other researchers have their work cut out for them.

“It could be beneficial in early stages to activate microglia to eat up amyloid beta,” says Xu, “but if you over-activate them, they may release an overabundance of cytokines (causing extensive inflammation) damaging healthy synaptic junctions as a side-effect from overactivation.”

Still, the ability to use the brain’s existing immune mechanisms to clear amyloid offers intriguing possibilities.

“Going after microglia, rather than amyloid beta generation, may be a new research avenue for Alzheimer’s disease,” says Xu. “We could use brain immune cells to solve what’s becoming a public health crisis.”


Explore further:
One step closer to defeating Alzheimer’s disease

More information:
Neuron (2018). DOI: 10.1016/j.neuron.2018.01.031

Neuron (2018). DOI: 10.1016/j.neuron.2018.02.002

Journal reference:
Neuron

Provided by:
Sanford-Burnham Prebys Medical Discovery Institute

Tagged with:

About author

Related Articles