ABSTRACT
Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated declines in ribose 5-phosphate. In vitro, Trem1-deficient microglia are resistant to amyloid-ß42 oligomer-induced bioenergetic changes, suggesting that amyloid-ß42 oligomer stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD mouse model, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy and changes in the disease-associated microglial transcriptomic signature. In aging APPSwe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. In postmortem Alzheimer disease brain, TREM1 colocalizes with Iba1+ cells around amyloid plaques and its expression is associated with Alzheimer disease clinical and neuropathological severity. Our results suggest that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology.
Subject(s)
Aging , Alzheimer Disease , Disease Models, Animal , Energy Metabolism , Microglia , Triggering Receptor Expressed on Myeloid Cells-1 , Animals , Mice , Aging/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Cognition/physiology , Energy Metabolism/physiology , Hippocampus/metabolism , Hippocampus/pathology , Mice, Inbred C57BL , Mice, Transgenic , Microglia/metabolism , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Triggering Receptor Expressed on Myeloid Cells-1/geneticsABSTRACT
Objetivo: Describir una serie de casos de fracturas de cóndilo mandibular resueltas por abordaje intraoral y asistencia video-endoscópica. Casos clínicos: Se presentan 3 casos de pacientes con fracturas de cóndilo mandibular unilateral. Dos casos presen- tan un segundo trazo de fractura parasinfisiaria asociada. El tratamiento realizado fue la reducción abierta y la fijación in- terna de todas las fracturas por abordaje oral. Se realizaron controles clínicos y tomográficos mediatos y a distancia (AU)
Aim: To present the experience with a series of cases re- solved by an intraoral approach and video-endoscopic assis- tance for the management of mandibular condyle fractures. Clinical cases: Three cases of patients with unilater- al mandibular condyle fractures are presented. Two of the cases presented a second line of associated parasymphyseal fracture. The treatment performed was open reduction and internal fixation of all fractures by oral approach. Mid-term and long-term clinical and tomographic follow-ups were per- formed, with favorable results (AU)
