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P1‐186: IMPAIRED β‐GLUCOCEREBROSIDASE ACTIVITY AND PROCESSING IN FRONTOTEMPORAL DEMENTIA DUE TO PROGRANULIN MUTATIONS
Author(s) -
Arrant Andrew E.,
Boyle Nicholas R.,
Roth Jonathan R.,
Li Alissa Nana,
Spina Salvatore,
Grinberg Lea T.,
Miller Bruce L.,
Seeley William W.,
Roberson Erik D.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.741
Subject(s) - frontotemporal dementia , glucocerebrosidase , biology , lysosome , mutation , frontotemporal lobar degeneration , loss function , medicine , endocrinology , enzyme , genetics , phenotype , biochemistry , dementia , gene , disease
and subsets of brain vascular endothelial cells. Phospho-tau positive dystrophic neurites were associated with PGRN structures, but we did not observe PGRN positive neurofibrillary tangles. There was significant increase in PGRN protein levels in AD compared to LP and HP cases by western blot, with significant correlation between PGRN and tangle scores but not plaque scores. In 2/3 FTLD cases, PGRN-positive microglia were observed, particularly in white matter. Conclusions: The role of PGRN in AD is still unclear as levels are increased. Activated microglia have increased amounts of anti-inflammatory PGRN, and most Ab plaques are PGRN-positive. The consequence of early deposits of PGRN on Ab plaques asks the question whether PGRN is promoting the formation of plaques or aiding in their removal by microglia.