Neurodegeneration Models and Therapeutic Strategies in Alzheimer's Disease

Alzheimer’s disease is defined by the progressive loss of neurons and synapses, driven primarily by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau. A diverse array of experimental models—from simple organisms to sophisticated mammalian systems—has been developed to unravel the molecular underpinnings of neurodegeneration and to evaluate candidate therapies. Invertebrate models such as yeast, Caenorhabditis elegans and Drosophila melanogaster offer rapid genetic screening of pathways that govern proteostasis, oxidative stress responses and chaperone activity. Rodent transgenic lines carrying human Aβ or tau mutations provide insights into synaptic dysfunction, neuroinflammation and cognitive decline. Emerging three-dimensional cultures and induced pluripotent stem cell-derived neurons recapitulate aspects of human brain architecture, enabling high-content drug screening. Therapeutic strategies under investigation include small molecules that stabilise native protein conformations or inhibit oligomer formation; passive and active immunotherapies targeting Aβ or tau; modulators of lipid metabolism and mitochondrial function; and novel neuroprotective agents derived from natural products. Advances in omics technologies have refined biomarker discovery and patient stratification, while gene-editing approaches hold promise for long-term correction of genetic risk factors. Together, these models and strategies form an integrated pipeline for translating basic discoveries into clinical interventions aimed at slowing, halting or reversing Alzheimer’s pathology.

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Neurodegeneration Models and Therapeutic Strategies in Alzheimer's Disease publication trend

The graph below shows the total number of articles in neurodegeneration models and therapeutic strategies in alzheimer's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Amyloid-beta (Aβ): A peptide fragment prone to misfolding and aggregation, forming extracellular plaques in Alzheimer’s disease.

Tau protein: A microtubule-associated protein that, when hyperphosphorylated, aggregates into intracellular neurofibrillary tangles.

Proteostasis: The cellular network of pathways that govern protein folding, quality control and degradation.

Transgenic model: An organism genetically engineered to express foreign genes, often used to mimic human disease processes.

Transcriptomics: The large-scale analysis of RNA transcripts to assess gene expression patterns.

Metabolomics: The comprehensive study of small-molecule metabolites within cells or organisms.

Neuroprotection: Strategies or agents that preserve neuronal structure and function against pathological insults.

Oxidative stress: A condition arising from an imbalance between reactive oxygen species production and antioxidant defences.

References

1. Simple model systems reveal conserved mechanisms of Alzheimer’s disease and related tauopathies. Molecular Neurodegeneration (2023).
2. In vivo neuroprotective capacity of a Dunaliella salina extract - comprehensive transcriptomics and metabolomics study. npj Science of Food (2024).
3. Omics approaches to investigate the neuroprotective capacity of a Citrus sinensis (sweet orange) extract in a Caenorhabditis elegans Alzheimer’s model. Food Research International (2023).