@article{fb0b99462bac47949350972ad0ad7fcc,
title = "FTLD-TDP with and without GRN mutations cause different patterns of CA1 pathology",
abstract = "Heterozygous loss-of-function mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A). PGRN is a highly conserved, secreted glycoprotein and functions in the central nervous system as a key modulator of microglial function. Hence, altered microglial function caused by PGRN deficiency may be tied to the pathogenesis of FTLD-TDP. Our previous studies showed that haploinsufficiency of GRN mutations extends to microglial PGRN expression in the hippocampal CA1 region. In this study, we found that the CA1 sector was associated with less neuronal loss and more frequent TDP-43 inclusions in FTLD-TDP type A cases with GRN mutations than in sporadic cases. In addition, the CA1 region in GRN mutation cases contained more rod-like microglia, which also had reduced PGRN expression. These findings suggest that the profile of TDP-43 inclusions, neuronal number, and microgliosis in the CA1 sector of FTLD-TDP type A cases may be influenced by GRN gene expression status.",
keywords = "Frontotemporal lobar degeneration, Hippocampal sclerosis, Microglia, Neuroinflammation, Progranulin, TAR DNA-binding protein 43",
author = "Qinwen Mao and Xiaojing Zheng and Tamar Gefen and Emily Rogalski and Spencer, {Callen L.} and Rosa Rademakers and Fought, {Angela J.} and Missia Kohler and Sandra Weintraub and Haibin Xia and Mesulam, {Marek Marsel} and Bigio, {Eileen H.}",
note = "Funding Information: This study was supported by the Alzheimer?s Disease Research Fund Grant (83282003F and 93282003G) from the Illinois Department of Public Health (to Q.M.), an Alzheimer?s Disease Core Center grant (P30 AG013854) from the National Institute on Aging to Northwestern University, Chicago, Illinois (R01 DC008552 to M.M.), (R35 NS097261 to R.R.), as well as research grants from the National Natural Science Foundation of China (81471772 and 81773265 to H.X.) and the Fundamental Research Funds for the Central Universities (GK201706002 to H.X.). Funding Information: From the Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (QM, EHB); Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi{\textquoteright}an, Shaanxi, P.R. China (XZ, HX); Mesulam Center for Cognitive Neurology and Alzheimer{\textquoteright}s Disease, Northwestern University Feinberg School of Medicine, Chicago, Illinois (TG, ER, CLS, SW, M-MM, EHB); Department of Neuroscience, Mayo Clinic, Jacksonville, Florida (RR); Division of Biostatistics, Department of Pre-ventive Medicine, Northwestern University Feinberg School of Medicine (AJF); and Cook County Medical Examiner, Chicago, Illinois (MK) Send correspondence to: Qinwen Mao, MD, PhD, Northwestern University Feinberg School of Medicine, 710 N Fairbanks Ct., Olson 2-458, Chi-cago, IL 60611; E-mail: q-mao@northwestern.edu This study was supported by the Alzheimer{\textquoteright}s Disease Research Fund Grant (83282003F and 93282003G) from the Illinois Department of Public Health (to Q.M.), an Alzheimer{\textquoteright}s Disease Core Center grant (P30 AG013854) from the National Institute on Aging to Northwestern Uni-versity, Chicago, Illinois (R01 DC008552 to M.M.), (R35 NS097261 to R.R.), as well as research grants from the National Natural Science Foun-dation of China (81471772 and 81773265 to H.X.) and the Fundamental Research Funds for the Central Universities (GK201706002 to H.X.). Publisher Copyright: {\textcopyright} 2019 American Association of Neuropathologists, Inc. All rights reserved.",
year = "2019",
month = sep,
day = "1",
doi = "10.1093/jnen/nlz059",
language = "English (US)",
volume = "78",
pages = "844--853",
journal = "Journal of neuropathology and experimental neurology",
issn = "0022-3069",
number = "9",
}