ArticleActa neuropathologica communications2020
The unfolded protein response is activated in the olfactory system in Alzheimer's disease.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Neuropathology in chronic traumatic encephalopathy: a systematic review of comparative post-mortem histology literature.Acta neuropathologica communications · 2022Pooled it
- Brain Activities Responding to Acupuncture at ST36 (Frontiers in neurology · 2022Pooled it
- High-field MRI correlates with immunohistochemical analysis of the normal and Alzheimer's disease anterior olfactory nucleus.NeuroImage · 2026Article
- Role of Sigma-1 Receptors in the Paraventricular Nucleus and Myocardium during Cirrhotic Cardiomyopathy in Rats.Molecular neurobiology · 2026Article
- Is dolichol pathway dysfunction a significant factor in Alzheimer's disease?Inflammopharmacology · 2025Review
- Huntingtin inclusion bodies have distinct immunophenotypes and ubiquitination profiles in the Huntington's disease human cerebral cortex.Scientific reports · 2025Article
- Brain iron accumulation in neurodegenerative disorders: Does air pollution play a role?Particle and fibre toxicology · 2025Article
- Seneca Valley virus induces mitochondrial apoptosis by activating ER stress or the PERK pathway based on CaJournal of virology · 2025Article
- Neuronal TDP-43 aggregation drives changes in microglial morphology prior to immunophenotype in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Visualizing the human olfactory projection and ancillary structures in a 3D reconstruction.Communications biology · 2024Article
- Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study.Neurotrauma reports · 2024Article
- Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice.Molecular and cellular biology · 2024Article
- Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain.Acta neuropathologica communications · 2023Article
- Progressive Spread of Beta-amyloid Pathology in an Olfactory-driven Amyloid Precursor Protein Mouse Model.Neuroscience · 2023Article
- Exercise suppresses neuroinflammation for alleviating Alzheimer's disease.Journal of neuroinflammation · 2023Review
- Non-Invasive Nasal Discharge Fluid and Other Body Fluid Biomarkers in Alzheimer's Disease.Pharmaceutics · 2022Review
- Impaired insulin signalling and allostatic load in Alzheimer disease.Nature reviews. Neuroscience · 2022Review
- Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer's disease.Acta neuropathologica communications · 2022Article
- Targeting the Unfolded Protein Response as a Disease-Modifying Pathway in Dementia.International journal of molecular sciences · 2022Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Olfactory dysfunction is an early and prevalent symptom of Alzheimer's disease (AD) and the olfactory bulb is a nexus of beta-amyloid plaque and tau neurofibrillary tangle (NFT) pathology during early AD progression. To mitigate the accumulation of misfolded proteins, an endoplasmic reticulum stress response called the unfolded protein response (UPR) occurs in the AD hippocampus. However, chronic UPR activation can lead to apoptosis and the upregulation of beta-amyloid and tau production. Therefore, UPR activation in the olfactory system could be one of the first changes in AD. In this study, we investigated whether two proteins that signal UPR activation are expressed in the olfactory system of AD cases with low or high amounts of aggregate pathology. We used immunohistochemistry to label two markers of UPR activation (p-PERK and p-eIF2α) concomitantly with neuronal markers (NeuN and PGP9.5) and pathology markers (beta-amyloid and tau) in the olfactory bulb, piriform cortex, entorhinal cortex and the CA1 region of the hippocampus in AD and normal cases. We show that UPR activation, as indicated by p-PERK and p-eIF2α expression, is significantly increased throughout the olfactory system in AD cases with low (Braak stage III-IV) and high-level (Braak stage V-VI) pathology. We further show that UPR activation occurs in the mitral cells and in the anterior olfactory nucleus of the olfactory bulb where tau and amyloid pathology is abundant. However, UPR activation is not present in neurons when they contain NFTs and only rarely occurs in neurons containing diffuse tau aggregates. We conclude that UPR activation is prevalent in all regions of the olfactory system and support previous findings suggesting that UPR activation likely precedes NFT formation. Our data indicate that chronic UPR activation in the olfactory system might contribute to the olfactory dysfunction that occurs early in the pathogenesis of AD.
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