Photomicrographs display hematoxylin-eosin staining DRG neurons from young and old GLA KO and WT mice (A–D) and exemplified measured cell area (yellow circles). (E) Quantification of neuronal cell area revealed increased cell size in young GLA KO compared to young WT mice (p<0.01) and in old GLA KO compared to young GLA KO and old WT mice (p<0.001 each). Photomicrographs show toluidin blue staining (F–I) of 0.5 µm semithin sections of dorsal root ganglia (DRG) from young (3 months) and old (≥12 months) wildtype (WT) and α-galactosidase A deficient (GLA KO) mice. Additionally, photomicrographs display immunoreactivity of antibodies against CD77 as a marker for globotriaosylceramide (Gb3) (J–M) and against binding immunoglobulin protein (BiP) (N–O) on 10 µm cryosections of DRG of old GLA KO and WT mice. No deposits were found in DRG neurons of young WT mice (F, arrow), neurons of a young GLA KO mice showed few intraneuronal deposits (G, arrowheads). Similar to young WT mice, there were no deposits in DRG neurons of old WT mice (H, arrow). Old GLA KO mice, however, displayed many deposits in DRG neurons (I, arrowheads). Gb3 load was not different between young GLA KO, young WT, and old WT mice (J–M), while old GLA KO mice displayed increased Gb3 accumulation in DRG neurons (M, arrows) and extraneural structures (M, arrowheads). BiP was homogeneously expressed in DRG neurons of old WT mice sparing the nucleus (N, arrows). Neurons of old GLA KO mice showed increased accumulation of BiP around the nucleus, indicating accumulation in the endoplasmic reticulum (O, arrows). GLA KO: young (3 months; hematoxylin-eosin: male; toluidine: female; CD77: male), old (≥12 months; hematoxylin-eosin: female; toluidine: female; CD77: male). WT: young (3 months; hematoxylin-eosin: male; toluidine: female; CD77: male), old (≥12 months; hematoxylin-eosin: female; toluidine: male; CD77: male). Scale bar hematoxylin-eosin: 50 µm. Scale bar toloudin blue: 10 µm. Scale bar CD77: 50 µm. The non-parametric Mann-Whitney U test was applied for group comparison. **p<0.01; ***p<0.001.