Prodromal pathogenesis of CLN7 Batten Disease revealed by multimodal biomarkers in macaques

Liguore, W. A.; Hilven, W.; Lurye, L.; Akkermans, J.; Decrop, M.; Zweig, R.; Sherman, L. S.; McBride, J. L.; Bertoglio, D.; Weiss, A. R.

doi:10.64898/2025.12.02.691930

bioRxiv · 10.64898/2025.12.02.691930

Prodromal pathogenesis of CLN7 Batten Disease revealed by multimodal biomarkers in macaques

Liguore, W. A.·Hilven, W.·Lurye, L.·Akkermans, J.·Decrop, M.·Zweig, R.·Sherman, L. S.·McBride, J. L.·Bertoglio, D.·Weiss, A. R.

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Abstract

Neuronal ceroid lipofuscinosis type 7 (CLN7) is a devastating paediatric neurodegenerative disorder with no cure and limited natural history data to guide therapeutic development. Here, we present the first multimodal characterization of prodromal and early-stage CLN7 disease in Japanese macaques carrying a spontaneous CLN7-/- mutation. Using structural T2-weighted MRI for volumetry, [18F]FDG PET for glucose metabolism, and [11C]PBR28 PET for neuroinflammation, we observed region-dependent patterns in volumetric, molecular, and metabolic alterations. MRI confirmed the presence of disease-associated atrophy in many cortical and subcortical brain regions, consistent with human pathology, [18F]FDG PET revealed early cortical and subcortical widespread hypometabolism, and [11C]PBR28 PET imaging detected progressive neuroinflammation in the same brain areas. CSF analyses further showed age-dependent increases in neurofilament light (NfL), providing convergent evidence for neurodegeneration. Together, these results define a prodromal trajectory in CLN7 disease, establish sensitive imaging and fluid biomarkers, and validate the macaque model as a powerful platform for testing interventions.

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Liguore, W. A., Hilven, W., Lurye, L., Akkermans, J., Decrop, M., Zweig, R., Sherman, L. S., McBride, J. L., Bertoglio, D., Weiss, A. R.. 2025-12-05. Prodromal pathogenesis of CLN7 Batten Disease revealed by multimodal biomarkers in macaques. https://doi.org/10.64898/2025.12.02.691930

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