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Updated: Mar 28, 2026
Author Spotlight: Advancing Alzheimer's Research – Exploring Early Detection and Multi-Omics Approaches
Published on: December 15, 2023
Molecular links between early energy metabolism alterations and Alzheimer's disease
Ignacio Pedros1, Ivan Patraca1, Nohora Martinez1
1Unitats de Bioquimica i, i Ciencies de la Salut, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat Rovira i Virgili, C./St. Llorenç 21 43201 Reus (Tarragona), Spain.
Abstract:
Recent studies suggest that the neurobiology of Alzheimer's disease (AD) pathology could not be explained solely by an increase in beta-amyloid levels. In fact, success with potential therapeutic drugs that inhibit the generation of beta amyloid has been low. Therefore, due to therapeutic failure in recent years, the scientists are looking for alternative hypotheses to explain the causes of the disease and the cognitive loss. Accordingly, alternative hypothesis propose a link between AD and peripheral metabolic alteration. Then, we review in depth changes related to insulin signalling and energy metabolism in the context of the APPSwe/PS1dE9 (APP/PS1) mice model of AD. We show an integrated view of the changes that occur in the early stages of the amyloidogenic process in the APP/PS1 double transgenic mice model. These early changes affect several key metabolic processes related to glucose uptake and insulin signalling, cellular energy homeostasis, mitochondrial biogenesis and increased Tau phosphorylation by kinase molecules like mTOR and Cdk5.
Insights
Alzheimer's disease (AD) may stem from metabolic changes, not just beta-amyloid. Early metabolic alterations in the brain impact energy and insulin signaling, contributing to AD pathology and cognitive decline.
Area of Science:
- Neurobiology
- Metabolic disease
- Alzheimer's disease research
Background:
- Alzheimer's disease (AD) pathology is complex and not fully explained by beta-amyloid accumulation alone.
- Therapeutic strategies targeting beta-amyloid have shown limited success, necessitating alternative hypotheses.
- Emerging evidence suggests a link between AD and peripheral metabolic alterations.
Purpose of the Study:
- To investigate the role of metabolic alterations in the early stages of Alzheimer's disease (AD).
- To explore changes in insulin signaling and energy metabolism in a mouse model of AD.
- To provide an integrated view of early pathological changes in AD.
Main Methods:
- Utilized the APPSwe/PS1dE9 (APP/PS1) double transgenic mice model of AD.
- Analyzed early-stage changes associated with the amyloidogenic process.
- Examined key metabolic processes, including glucose uptake, insulin signaling, and energy homeostasis.
Main Results:
- Observed significant alterations in glucose uptake and insulin signaling pathways in APP/PS1 mice.
- Identified disruptions in cellular energy homeostasis and mitochondrial biogenesis.
- Found increased Tau phosphorylation mediated by kinases such as mTOR and Cdk5.
Conclusions:
- Early metabolic dysregulation is a critical factor in Alzheimer's disease (AD) pathogenesis.
- Changes in insulin signaling and energy metabolism precede or accompany amyloid pathology.
- Targeting metabolic pathways may offer novel therapeutic strategies for AD.
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