Astrocytic Activity and Neuroimaging in Alzheimer’s Disease

Astrocytes, the most abundant glial cell in the central nervous system, play a pivotal role in maintaining neural homeostasis, regulating synaptic transmission and supporting the blood–brain barrier. In Alzheimer’s disease (AD), these cells undergo a transformation known as reactive astrogliosis, characterised by changes in morphology, upregulation of glial fibrillary acidic protein (GFAP) and altered metabolic activity. Modern neuroimaging techniques, particularly positron emission tomography (PET) equipped with novel radiotracers, have enabled in vivo visualisation of astrocytic responses alongside classical hallmarks of AD such as amyloid-β and tau deposition. Multi-tracer approaches reveal that astrocytic activation often precedes overt plaque and tangle formation, suggesting a contributory role in disease onset and progression. Recent advances integrate fluid biomarkers (for example plasma GFAP) with PET measures of astrocyte-specific enzymes such as monoamine oxidase B (MAO-B), offering a more nuanced view of astrocyte heterogeneity. These developments carry global significance for early diagnosis, patient stratification in clinical trials and the design of astrocyte-targeted therapies aimed at modulating neuroinflammation and preserving neuronal integrity.

Research from Nature Portfolio

Early investigations using multi-tracer PET in individuals carrying autosomal dominant Alzheimer’s disease mutations have demonstrated that astrocyte activation emerges in the presymptomatic phase. Binding of an astrocyte-selective PET tracer increased markedly before the rise in amyloid tracer retention, indicating that reactive astrogliosis may serve as an initial driver in the cascade of pathological events. Complementary autoradiography studies of postmortem cortical tissue reveal a striking laminar co-distribution of activated astrocytes and tau deposits across temporal and frontal regions. The spatial concordance between elevated binding of a selective astrocyte ligand and tau pathology supports a close pathological interconnection and suggests that astrocytes might influence the regional vulnerability to tau aggregation.

Astrocytic Activity and Neuroimaging in Alzheimer’s Disease publication trend

The graph below shows the total number of articles in astrocytic activity and neuroimaging in alzheimer’s disease across all publications each year (not limited to Nature Index journals).

Technical terms

Astrocyte: A star-shaped glial cell that supports neurons, regulates neurotransmitter levels and maintains the blood–brain barrier.

Reactive astrogliosis: A defence response of astrocytes to injury or disease, marked by cellular hypertrophy, proliferation and upregulation of GFAP.

GFAP (glial fibrillary acidic protein): An intermediate filament protein used as a marker of astrocyte activation.

Positron emission tomography (PET): An imaging modality that uses radiolabelled tracers to visualise molecular processes in vivo.

Radiotracer: A radioactive compound designed to bind specifically to a molecular target, enabling its detection by PET.

Monoamine oxidase B (MAO-B): An enzyme highly expressed in reactive astrocytes; serves as a PET target for imaging neuroinflammation.

References

1. Tracking reactive astrogliosis in autosomal dominant and sporadic Alzheimer’s disease with multi-modal PET and plasma GFAP. Molecular Neurodegeneration (2023).
2. [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data. Journal of Neuroinflammation (2023).
3. Astrocyte Signature in Alzheimer’s Disease Continuum through a Multi-PET Tracer Imaging Perspective. Cells (2023).
4. Early astrocytosis in autosomal dominant Alzheimer’s disease measured in vivo by multi-tracer positron emission tomography. Scientific Reports (2015).
5. Cortical laminar tau deposits and activated astrocytes in Alzheimer’s disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography. Scientific Reports (2017).