Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease

Dysfunction of the endosomal-lysosomal network is a notable feature of Alzheimer's disease (AD) pathology. Dysfunctional endo-lysosomal vacuoles accumulate in dystrophic neurites surrounding amyloid beta (A beta) plaques and may be involved in the pathogenesis and progression of A beta aggregates. Trafficking and thus maturation of these dysfunctional vacuoles is disrupted in the vicinity of A beta plaques. Transmembrane protein 55B (TMEM55B), also known as phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1 (PIP4P1) is an endo-lysosomal membrane protein that is necessary for appropriate trafficking of endo-lysosomes. The present study tested whether overexpression of TMEM55B in the hippocampus could prevent plaque-associated axonal accumulation of dysfunctional endo-lysosomes, reduce A beta plaque load, and prevent hippocampal-dependent learning and memory deficits in the 5XFAD mouse models of A beta plaque pathology. Immunohistochemical analyses revealed a modest but significant reduction in the accumulation of endo-lysosomes in dystrophic neurites surrounding A beta plaques, but there was no change in hippocampal-dependent memory or plaque load. Overall, these data indicate a potential role for TMEM55B in reducing endo-lysosomal dysfunction during AD-like A beta pathology.