Researchers have developed engineered human microglia that detect disease-related brain changes and release therapeutic proteins precisely where needed.

The pair decided to conduct a clinical trial that could be more compelling. In 12 people with early Alzheimer’s who took 3TC for 6 months, the drug didn’t boost cognitive abilities. But other indicators suggested some benefits, as Frost, Sullivan, and their colleagues revealed last month in npj Dementia. For instance, levels of one key neurodegeneration indicator dipped, suggesting 3TC protects patients’ brain cells. “That was the change I was most excited to see,” Frost says.

Their recent study was the first clinical test of an antitransposon strategy for Alzheimer’s to reach the finish line. But it’s just one of a growing number of trials launched by academic researchers and biotechs to gauge the effects of throttling transposons—so-called jumping genes. These vagrant sequences, some of which are relics of viruses that invaded cells long ago or may even be derived from symbiotic bacteria, make up more than 40% of the human genome but were once seen as largely harmless. However, a variety of evidence from human cell lines, lab animals, and epidemiological studies has implicated their antics in illnesses such as lupus, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and cancer, as well as in aging.

Encouraging results are trickling in. In 2022, a phase 2 trial determined that 3TC halted tumor growth in some patients with colorectal cancer. Last year, Transposon Therapeutics revealed that a different drug that stymies replication of these sequences slowed one sign of physical decline in people with ALS or another neurodegenerative disease, frontotemporal dementia. “It’s really amazing how quickly the story has developed,” says John Sedivy, a molecular biologist at Brown and the company’s co-founder.

Measles cases are going up—and a federal scientist has warned that case counts have probably been underreported. Another vaccine-preventable illness, whooping cough, sees a troubling increase in cases. Ancient humans found sun-protection solutions when Earth’s magnetic poles wandered. A colossal squid has been captured on video in its natural habitat for the first time. Plus, we discuss evidence that Mars once had a carbon cycle and a planet that is orbiting a pair of brown dwarfs.

Episode Transcript: https://www.scientificamerican.com/po… reading: This Is the First Colossal Squid Filmed in the Deep Sea—And It’s a Baby! • See the first colossal squid ever cau… RFK, Jr., Is Wrong about Cause of Rising Autism Rates, Scientists Say https://www.scientificamerican.com/ar… How to Talk about Vaccines in an Era of Scientific Mistrust https://www.scientificamerican.com/ar… E-mail us at [email protected] if you have any questions, comments or ideas for stories we should cover! Discover something new every day: subscribe to Scientific American: https://www.scientificamerican.com/ge… And sign up for Today in Science, our daily newsletter: https://www.scientificamerican.com/ac… Science Quickly is produced by Rachel Feltman, Fonda Mwangi, Kelso Harper, Naeem Amarsy and Jeff DelViscio. This episode was hosted by Rachel Feltman. Our show is edited by Alex Sugiura with fact-checking by Shayna Posses and Aaron Shattuck. The theme music was composed by Dominic Smith.

Recommended reading:
This Is the First Colossal Squid Filmed in the Deep Sea—And It’s a Baby! • See the first colossal squid ever cau…
RFK, Jr., Is Wrong about Cause of Rising Autism Rates, Scientists Say https://www.scientificamerican.com/ar…
How to Talk about Vaccines in an Era of Scientific Mistrust https://www.scientificamerican.com/ar…

E-mail us at [email protected] if you have any questions, comments or ideas for stories we should cover!

Discover something new every day: subscribe to Scientific American: https://www.scientificamerican.com/ge…

Psychedelic drugs are seeing a surge of interest from mainstream medicine, and initial results suggest that psychedelic-therapy can be a safe and effective treatment for some mental health conditions. However, the side-effect profile is still incompletely understood. In particular, the use of psychedelics has been posited to carry a risk of triggering latent psychotic disorders or persistent visual hallucinations, known as hallucinogen persisting perception disorder (HPPD).

In order to better understand the prevalence and risk factors of such side-effects, Katie Zhou and colleagues surveyed 654 people online who were planning to take psychedelics through their own initiative. The findings are published in the journal PNAS Nexus.

Of the 654 people surveyed, 315 people were resurveyed two weeks after their experience and 212 people were resurveyed again four weeks after their experience. The sample was 74% male, and 77% university-educated. About one-third had been diagnosed with at least one psychiatric condition.

Recurring dreams may feature taking a test the dreamer didn’t study for, having to make a speech or being attacked. Here’s why our sleeping brain comes back to these unpleasant dreams again and again

This exercise “plays a crucial role in brain health, with increasing evidence linking it to a reduced risk of Alzheimer’s disease,” a doctor told Newsweek.

R&d and field deployment of orchestrated objective reduction

The metabolic fitness of microglia is markedly impaired in TREM2 knockout (KO) models [58]. TREM2, through its adaptors DAP12 and DAP10, activates the mechanistic target of rapamycin (mTOR) signaling pathway, which plays a crucial role in regulating metabolic pathways and protein synthesis [11, 58]. Loss of TREM2 impairs mTOR activation, leading to reduced ATP production and biosynthesis. In vivo FDG-PET imaging of TREM2 KO and TREM2 T66M knock-in mice shows a significant reduction in cerebral glucose metabolism [67, 68]. This decrease may correlate with impaired glucose uptake by microglia. Supporting this, ex vivo measurements of isolated microglia from TREM2 KO animals reveal lower FDG uptake [68].

Given the pivotal role of microglial metabolism in AD, targeting this process represents a promising therapeutic strategy. Agents such as interferon-γ (IFN-γ) and cyclocreatine, which enhance ATP production, have been shown to restore microglial functions and mitigate AD pathology [58, 65]. Notably, TREM2-activating antibodies boost microglial energy metabolism by promoting mitochondrial fatty acid and glucose oxidation [69]. Moreover, translocator protein (TSPO)-PET and FDG-PET imaging have demonstrated that TREM2 activation enhances microglial activity and glucose metabolism in amyloid mouse models. Thus, targeting TREM2 and microglial metabolism may complement existing AD therapies, which primarily focus on amyloid clearance and synaptic dysfunction, providing a more comprehensive approach to disease intervention.

Lipid metabolism is crucial for maintaining microglial functions and CNS homeostasis, influencing cellular membrane integrity, energy storage, and inflammatory responses. Emerging evidence identifies TREM2 as a key regulator of lipid metabolism in the brain. TREM2 binds a diverse range of lipids, including anionic and zwitterionic species such as sphingomyelin, phosphatidic acid, phosphatidylinositol, phosphatidylcholine, phosphatidylglycerol, phosphatidylserine (PtdSer) and sulfatide [49, 53, 70]. Among these, PtdSer is the most abundant negatively charged phospholipid in the inner leaflet of the plasma membrane in eukaryotic cells [71]. In neurodegenerative conditions, PtdSer externalization on damaged or apoptotic neurons serves as an “eat-me” signal, triggering TREM2-dependent microglial synaptic pruning and cell clearance [72]. Super-resolution microscopy and in vivo imaging studies have demonstrated that Aβ oligomer-induced hyperactive synapses expose PtdSer, marking them for TREM2-mediated engulfment, which helps mitigate neuronal hyperactivity in AD models. Additionally, individuals carrying TREM2 loss-of-function variants exhibit an accumulation of apoptotic-like synapses [72], underscoring TREM2’s essential role in synaptic homeostasis during early AD pathology. Beyond synaptic pruning, TREM2 facilitates the recognition and clearance of damaged cells. Notably, over-expression of TREM2 in non-phagocytic cells, such as Chinese hamster ovary (CHO) and HEK293 cells, enables them to engulf apoptotic neurons, highlighting TREM2’s function in lipid sensing and phagocytosis [16, 73]. This broad lipid-binding capability underscores TREM2’s critical role in modulating microglial responses to neurodegenerative insults and preserving neuronal health.

But to fully grasp the tools’ potential, we need to better understand how electric and magnetic fields interact with the brain.

Advances in brain imaging technology provide new and different information about the brain.