Imaging Techniques in Alzheimer's Disease Models

Imaging technologies have revolutionised the study of Alzheimer’s disease in preclinical settings by enabling direct visualisation of pathological hallmarks and functional alterations in rodent models. Positron emission tomography (PET) employs radioligands that selectively bind amyloid-β aggregates, tau fibrils or markers of neuroinflammation to quantify disease burden in vivo and monitor therapeutic response. Magnetic resonance imaging (MRI) provides high-resolution anatomical information, functional connectivity maps and specialised contrasts for detecting early deposition of oligomeric species. Optical modalities, including two-photon and light-sheet microscopy, allow longitudinal tracking of synaptic changes, microglial dynamics and plaque formation in living tissue. Cryogenic-electron microscopy (cryo-EM) has recently been applied to ex vivo fibrils isolated from transgenic brains, resolving atomic architectures of amyloid assemblies. By integrating these approaches, researchers can characterise molecular configurations, cellular interactions and network-level dysfunction, thereby refining model selection and accelerating translation of novel diagnostics and therapies.

Research from Nature Portfolio

Recent studies have employed cryo-EM to compare the structures of amyloid-β fibrils extracted from diverse transgenic mouse lines. This work revealed that certain models harbour fibril conformations closely resembling those found in sporadic Alzheimer’s disease, underscoring the importance of matching fibril architecture when evaluating plaque-targeting tracers and therapeutics. In parallel, advances in antibody-based PET have harnessed receptor-mediated transcytosis to deliver high-affinity monoclonal antibodies across the blood–brain barrier. Conjugation of an amyloid-β antibody to a transferrin receptor ligand enabled robust brain uptake and age-dependent PET signals that correlated tightly with plaque load, demonstrating the feasibility of using antibody ligands for sensitive in vivo imaging and longitudinal assessment of immunotherapy efficacy.

Imaging Techniques in Alzheimer's Disease Models publication trend

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

Technical terms

Positron emission tomography (PET): A molecular imaging modality using positron-emitting tracers to quantify regional distribution of biomarkers in vivo.

Fluorodeoxyglucose (FDG): A glucose analogue labelled with ^18F used in PET to assess cerebral glucose metabolism.

Cryogenic-electron microscopy (cryo-EM): A technique that images flash-frozen specimens at cryogenic temperatures to determine high-resolution structures of macromolecules.

Transferrin receptor-mediated transcytosis: A strategy for ferrying therapeutic or imaging agents across the blood–brain barrier via engagement of endogenous iron transport pathways.

Metabolic connectivity: Correlation patterns of metabolic activity between brain regions, often derived from PET data, reflecting functional network integrity.

Aptamer contrast agent: A small nucleic acid ligand conjugated to an imaging reporter (such as gadolinium) that binds selectively to molecular targets, enhancing MRI signal.

References

1. Cryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer’s disease. Nature Neuroscience (2023).
2. Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer’s disease. Nature Communications (2016).
3. Depletion and activation of microglia impact metabolic connectivity of the mouse brain. Journal of Neuroinflammation (2023).
4. Brain metabolic network covariance and aging in a mouse model of Alzheimer's disease. Alzheimer's & Dementia (2023).
5. Oligomeric amyloid-β targeted contrast agent for MRI evaluation of Alzheimer’s disease mouse models. Frontiers in Pharmacology (2024).