Intraventicular Delivery of IL‐27 Gene Exerts Neuroprotection and Ameliorates Cognitive Deficits in A Mouse Model for Alzheimer's Disease
Year: 2025
Type: article
Abstract: BACKGROUND: Alzheimer's disease (AD) is a major challenge for the global public health system. AD is the most common (60-70%) type of dementia. Understanding the pathogenesis of AD is vital in developing effective, therapeutic or preventive strategies. The successful completion of a few late phase clinical trials and approval of monoclonal antibodies against amyloid protein in recent years reinforced the amyloid cascade hypothesis (ACH). However, the marginal efficacies of anti-amyloid therapy and its high frequencies of side effects (e.g: ARIA-E and AIRA-H) indicate other major player(s) in the pathogenesis of AD and warrant more effective, safer therapies. METHOD: In the current study, we generated recombinant Adeno-Associated Virus (rAAV) vector expressing mouse IL-27 (AAV-IL-27), enhanced green fluorescent protein (AAV-EGFP) and Control vector (AAC-Ctrl) without IL-27 cDNA. AAV-IL-27, AAV-EGFP or AAV-Ctrl were delivered by stereotactic injections into the lateral ventricles of Alzheimer's disease 5xFAD mice. Mice were monitored and evaluated for various durations after a single delivery of treatment, from 4 to 7.5 months. RESULT: Using flow cytometry and immunohistochemistry staining, we showed that intraventricular delivery of AAV-IL-27 successfully transduced neurons () with high levels of IL-27 expression. Meanwhile, enhanced expression of IL-27R were evident in regions such as the hippocampus and cerebral cortex. 5xFAD mice treated with AAV-IL-27 had preserved neuro-cognitive function as revealed by neurobehavioral tests. Furthermore, AAV-IL-27 treatment was found to reduce the expression of pro-inflammatory cytokine IL-1 and limit neuronal synaptic damage. CONCLUSION: Together with our previous reported findings, data from the current study suggest an intrinsic, neuroprotective pathway of IL-27 that alleviates neuronal damage associated with AD via modulation of the inflammatory responses within the CNS.
Source: Alzheimer s & Dementia
Author: Zichun Xiao
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W7117120543
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