Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Associated with the CSF1R p. (Ile843Thr) Variant: Clinical, Imaging, and Molecular Characterization

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a microgliopathy caused by pathogenic CSF1R variants. We report the first Japanese case of ALSP harboring the CSF1R p. (Ile843Thr) variant. The patient presented with progressive cognitive and behavioral decline followed by motor dysfunction, and MRI showed frontoparietal-predominant white matter lesions and corpus callosum thinning. A functional analysis demonstrated impaired autophosphorylation of the mutant protein, confirming pathogenicity. This case expands the CSF1R variants spectrum of ALSP and highlights the diagnostic value of integrating genetic testing with functional validation in adult-onset leukoencephalopathies, even when family history is absent.