Recent research findings have unveiled an intriguing revelation: an upsurge in hippocampal metabolism emerges as an early harbinger of Alzheimer’s disease, offering a potential breakthrough in early diagnosis and novel avenues for intervention. This breakthrough may usher in early-stage treatments aimed at targeting cellular energy and waste management processes, thereby decelerating the progression of this debilitating ailment.
Scientists hailing from the Karolinska Institute have identified an increase in metabolic activity within the hippocampus as an early stage in the development of Alzheimer’s disease, as disclosed in a study published in Molecular Psychiatry. This discovery paves the way for prospective methods of early intervention.
Alzheimer’s disease, the most prevalent form of dementia, affects approximately 20,000 individuals in Sweden each year. Researchers now posit that an escalation in metabolic activity within the mitochondria, the cellular powerhouses, serves as an early indicator of the disease.
Animal Models and Insights into Pathology
To unravel the intricacies of this phenomenon, research teams employed mice that exhibited Alzheimer’s disease pathology in a manner akin to humans. Notably, the augmented metabolism observed in young mice was subsequently accompanied by synaptic alterations, attributed to disruptions in the cellular recycling system, known as autophagy—a discovery honored with the Nobel Prize in Physiology or Medicine in 2016.
Over time, metabolism within the Alzheimer’s-afflicted brain generally declines, contributing to synaptic degradation. This decline was also discernible in older mice with a longer history of the disease.
Diagnostic Prospects and Metabolic Shifts
“The disease begins to manifest 20 years before the onset of symptoms, underscoring the importance of early detection, especially in light of the emergence of disease-slowing medications,” emphasizes Per Nilsson, associate professor at the Department of Neurobiology, Care Sciences, and Society at the Karolinska Institute. “Metabolic alterations could serve as a diagnostic criterion for this purpose.”
Maria Ankarcrona, a professor at the same department, adds, “Notably, changes in metabolism manifest prior to the accumulation of characteristic insoluble plaques in the brain. The observed shifts in energy balance align with our previous observations in Alzheimer’s brain imaging, but we have now detected these changes at an earlier stage.”
Methodology and Future Research
The study was conducted through a close collaboration between the two research groups, focusing on the hippocampus—a brain region crucial for short-term memory and an early target in the pathological progression of Alzheimer’s disease. Employing RNA sequencing to discern active genes within hippocampal cells at various stages of the disease, researchers identified heightened mitochondrial metabolism as an early-stage phenomenon.
Researchers scrutinized synaptic changes that ensued, employing electron microscopy and other techniques. They observed the accumulation of vesicles called autophagosomes within synapses, where spent proteins are broken down and their components metabolized, impeding access to functional proteins.
Subsequently, the researchers will delve deeper into the roles of mitochondria and autophagy in the development of Alzheimer’s disease. This research will include investigations in mice models that offer an even more accurate representation of the Alzheimer’s-affected brain.
“These findings underscore the significance of preserving functional mitochondria and normal protein metabolism,” states Dr. Nilsson. “In the future, we will conduct experiments on mice to evaluate the potential of new compounds that can stabilize mitochondrial and autophagic functions, potentially retarding the progression of the disease.”
Reference: “Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models” by Luana Naia, Makoto Shimozawa, Erika Bereczki, Xidan Li, Jianping Liu, Richeng Jiang, Romain Giraud, Nuno Santos Leal, Catarina Moreira Pinho, Erik Berger, Victoria Lim Falk, Giacomo Dentoni, Maria Ankarcrona and Per Nilsson, 32 October 2023, Molecular Psychiatry. DOI: 10.1038/s41380-023-02289-4
The study received financial support from the Swedish Research Council, the Swedish Alzheimer’s Foundation, and the Swedish Brain Fund, along with contributions from private donors. The researchers have disclosed no conflicts of interest.
Table of Contents
Frequently Asked Questions (FAQs) about Alzheimer’s Metabolism Discovery
What does the research reveal about Alzheimer’s disease?
The research uncovers that an increase in hippocampal metabolism serves as an early sign of Alzheimer’s disease, potentially enabling early diagnosis and novel intervention strategies.
How significant is this discovery?
This discovery is of paramount significance as it opens the door to potential early-stage treatments that target cellular energy and waste management processes to slow the progression of Alzheimer’s disease.
Why is early detection crucial for Alzheimer’s disease?
Early detection is vital because the disease begins to develop 20 years before symptoms appear. Identifying it early can be instrumental, especially with the emergence of disease-slowing medications.
What role do mitochondria play in Alzheimer’s disease?
Mitochondria, the cellular powerhouses, exhibit increased metabolism in the early stages of Alzheimer’s, making them a key focus for potential interventions.
How was this research conducted?
The study involved the use of mice models that mimic Alzheimer’s pathology in humans. Researchers employed advanced techniques, including RNA sequencing and electron microscopy, to investigate metabolic changes and synaptic disruptions.
What funding supported this research?
This research received funding from the Swedish Research Council, the Swedish Alzheimer’s Foundation, and the Swedish Brain Fund, as well as private donations. No conflicts of interest were reported by the researchers.
More about Alzheimer’s Metabolism Discovery
- Molecular Psychiatry Study: The full research article published in Molecular Psychiatry.
- Karolinska Institute: Information about the Karolinska Institute, where the research was conducted.
- Swedish Research Council: The Swedish Research Council, which provided funding for the study.
- Swedish Alzheimer’s Foundation: The Swedish Alzheimer’s Foundation, a source of funding for Alzheimer’s research.
- Swedish Brain Fund: The Swedish Brain Fund, another contributor to the research.
- Nobel Prize in Physiology or Medicine 2016: Information about the Nobel Prize awarded for autophagy research.
5 comments
Alzheimer’s is tough, but this study, big deal! mitochondria stuff, vry interestin!
Alzheimer’s 20 yrs b4 symptoms? serious stuff, need more tests & interventions
oh wow, they found early sign for Alzheimer’s disease? that’s gr8, so important for ppl! hope more research help
early detection imp, glad they look @ metabolism, early treatments sound hopeful!
This doesn’t relate to cars at all, but Alzheimer’s is imp, so good read!