Early Signs of Alzheimer’s: Hyperactive Metabolism in the Hippocampus

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Early Signs of Alzheimer’s: Hyperactive Metabolism in the Hippocampus

Early Signs of Alzheimer’s: Hyperactive Metabolism in the Hippocampus

New research has identified an increased metabolism in the hippocampus as an early sign of Alzheimer’s disease, potentially offering a new pathway for early diagnosis and intervention.

This discovery could inspire early treatments targeting cellular energy and waste management processes to slow the progression of the disease.

Early Signs of Alzheimer’s: Hyperactive Metabolism in the Hippocampus

A study published in “Molecular Psychiatry” by researchers at the Karolinska Institute reveals that increased metabolism in the hippocampus marks the early stages of Alzheimer’s disease.

This finding paves the way for potential early intervention methods.

Alzheimer’s is the most common form of dementia, affecting around 20,000 people in Sweden annually.

Researchers have now found that increased metabolism in the cell powerhouses, mitochondria, serves as an early indicator of the disease.

The pathological process in mice afflicted with Alzheimer’s is similar to that in humans. After an increase in metabolism in young mice, the cell recycling system, a process known as autophagy, is disrupted, leading to changes in synapses—an observation that earned the Nobel Prize in Physiology or Medicine in 2016.

Over time, the metabolism in the brains of Alzheimer’s patients typically decreases, resulting in synaptic degeneration.

Researchers also observed this in older mice with prolonged disease duration.

Diagnostic Potential and Metabolic Changes

Per Nilsson, Associate Professor of Neurobiology, Care Sciences, and Society at the Karolinska Institute, stated, “This disease starts developing 20 years before symptoms appear, so early detection is crucial—especially considering the emerging delayed drugs. Changes in metabolism might be one diagnostic factor.”

Maria Ankarcrona, a professor in the department, added, “Interestingly, changes in metabolism can be seen before any characteristic insoluble plaques accumulate in the brain. Different energy balances align with what we see in brain images of Alzheimer’s patients, but now we’re detecting these changes in earlier stages.”

Research Methods and Future Studies

This study, a collaboration between two research groups, analyzed a part of the mouse brain known as the hippocampus, a structure crucial in short-term memory and affected early in the pathological process.

Researchers used RNA sequencing to observe which genes in hippocampal cells were active during different disease stages, finding that one early stage of the disease involved increased mitochondrial metabolism.

Using electron microscopy and other techniques, researchers studied subsequent changes between brain neurons, discovering the accumulation of vesicles called autophagosomes in synapses. These vesicles are used to break down used proteins and metabolize their components, disrupting the acquisition of functional proteins.

Researchers aim to delve deeper into the role of mitochondria and autophagy in the development of Alzheimer’s disease, particularly in mouse studies providing a better model of the Alzheimer’s brain.

Dr. Nilsson noted, “These findings underscore the importance of maintaining mitochondrial function and normal protein metabolism. Looking ahead, we’ll be able to experiment in mice to observe if new molecules stabilizing mitochondrial and autophagic functions can delay the onset of the disease.”