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Association of Retromer Deficiency and Tau Pathology in Down Syndrome
Author(s) -
Curtis Mary Elizabeth,
Smith Tiffany,
Yu Daohai,
Praticò Domenico
Publication year - 2022
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26321
Subject(s) - retromer , association (psychology) , medicine , pathology , psychology , endosome , receptor , psychotherapist
Retromer deficiency is reported in Down syndrome and correlates with amyloidosis, however, its association with tau neuropathology remains unclear. Down syndrome and control brain tissues were evaluated for phosphorylated tau, tau modulators, and cathepsin‐D activity. Several kinases and phosphatase PP2A were unchanged, but tau phosphorylation was elevated, and cathepsin‐D activity decreased in aged patients with Down syndrome. Retromer proteins positively associated with soluble tau, whereas pathogenic tau negatively correlated with retromer proteins and cathepsin‐D activity. Retromer deficiency and consequent reduction of cathepsin‐D activity may contribute to pathogenic tau accumulation, thus, retromer represents a viable therapeutic target against tau pathology in Down syndrome. ANN NEUROL 2022;91:561–567