Kristian F. Odfalk, Jessica L. Wickline, Sabrina Smith, Radek Dobrowolski, Sarah C. Hopp
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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 β (Aβ) plaques and may be involved in the pathogenesis and progression of Aβ aggregates. Trafficking and thus maturation of these dysfunctional vacuoles is disrupted in the vicinity of Aβ 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 Aβ plaque load, and prevent hippocampal-dependent learning and memory deficits in the 5XFAD mouse models of Aβ plaque pathology. Immunohistochemical analyses revealed a modest but significant reduction in the accumulation of endo-lysosomes in dystrophic neurites surrounding Aβ 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 Aβ pathology.
期刊介绍:
Hippocampus provides a forum for the exchange of current information between investigators interested in the neurobiology of the hippocampal formation and related structures. While the relationships of submitted papers to the hippocampal formation will be evaluated liberally, the substance of appropriate papers should deal with the hippocampal formation per se or with the interaction between the hippocampal formation and other brain regions. The scope of Hippocampus is wide: single and multidisciplinary experimental studies from all fields of basic science, theoretical papers, papers dealing with hippocampal preparations as models for understanding the central nervous system, and clinical studies will be considered for publication. The Editor especially encourages the submission of papers that contribute to a functional understanding of the hippocampal formation.