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Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.
Alzheimers Dement
December 2024
Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.
Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).
Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.
Elevated expression of the retrotransposon LINE-1 drives Alzheimer's disease-associated microglial dysfunction.
Acta Neuropathol
November 2024
Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.
Article Synopsis
- * Researchers found increased levels of LINE-1 protein (ORF1p) in microglia from LOAD patients, which correlated with changes in microglial shape associated with the disease.
- * Gene editing experiments showed that activating LINE-1 in lab-developed microglia altered their functions and gene expression, hinting that LINE-1 activity may play a significant role in microglial dysfunction and the development of Alzheimer's disease.
Ageing-Related Macrophage Polarisation in the Trigeminal Ganglion Enhances Incisional Intraoral Pain.
Oral Dis
October 2024
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Article Synopsis
- Age-related changes in macrophage polarization in the trigeminal ganglion (TG) contribute to increased sensitivity to intra-oral pain after mucosal incisions, particularly in older SAMP8 mice compared to younger SAMR1 mice.
- The study involved measuring pain thresholds and analyzing the presence of specific inflammatory macrophage types (M1 and M2) in the TG over a period of 21 days post-injury.
- Results showed that enhanced CCL2 signaling from M1-macrophages in older mice led to greater pain hypersensitivity, indicating a link between aging, macrophage activity, and prolonged pain response.
Genetic removal of Nlrp3 protects against sporadic and R345W Efemp1-induced basal laminar deposit formation.
bioRxiv
October 2024
Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6 St. SE, Minneapolis, Minnesota, 55455, United States.
Chronic, unresolved inflammation has long been speculated to serve as an initiating and propagating factor in numerous neurodegenerative diseases, including a leading cause of irreversible blindness in the elderly, age-related macular degeneration (AMD). Intracellular multiprotein complexes called inflammasomes in combination with activated caspases facilitate production of pro-inflammatory cytokines such as interleukin 1 beta. Specifically, the nucleotide-binding oligomerization (NOD)-like receptor protein 3 (NLRP3) has received heightened attention due to the wide range of stimuli to which it can respond and its potential involvement in AMD.
View Article and Find Full Text PDFNicorandil treatment improves survival and spatial learning in aged granulin knockout mice.
Brain Pathol
October 2024
Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the "KATP" channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral performance, neuropathology, and gene expression.
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