Role of basal cells in nasal polyp epithelium in the pathophysiology of eosinophilic chronic rhinosinusitis (eCRS).

BACKGROUND: Basal cell hyperplasia is commonly observed in nasal polyp epithelium of eosinophilic chronic rhinosinusitis (eCRS). We examined the function and mechanisms of basal cell hyperplasia in the pathophysiology of eCRS. METHODS: We found that normal human bronchial epithelial (NHBE) cells obtained basal cell characteristics when cultured with PneumaCult™-Ex Plus Medium. Most of the cells passaged three times expressed basal cell surface markers CD49f and CD271 by flow cytometry, and basal cell nuclear marker p63 by immunohistochemical staining. We named these NHBE cells with basal cell characteristics cultured Basal-like cells (cBC), and NHBE cells cultured with BEGM™ cultured Epithelial cells (cEC). The characteristics of cBC and cEC were examined and compared by RNA sequencing, RT-PCR, ELISA, and cell proliferation studies. RESULTS: RNA sequencing revealed that cBC showed higher gene expression of thymic stromal lymphopoietin (TSLP), IL-8, TLR3, and TLR4, and lower expression of PAR-2 compared with cEC. The mRNA expression of TSLP, IL-8, TLR3, and TLR4 was significantly increased in cBC, and that of PAR-2 was significantly increased in cEC by RT-PCR. Poly(I:C)-induced TSLP production and LPS-induced IL-8 production were significantly increased in cBC. IL-4 and IL-13 stimulated the proliferation of cBC. Finally, the frequency of p63-positive basal cells was increased in nasal polyp epithelium of eCRS, and Ki67-positive proliferating cells were increased in p63-positive basal cells. CONCLUSIONS: Type 2 cytokines IL-4 and IL-13 induce basal cell hyperplasia, and basal cells exacerbate type 2 inflammation by producing TSLP in nasal polyp of eCRS.

Development of automatic generation system for lung nodule finding descriptions.

Worldwide, lung cancer is the leading cause of cancer-related deaths. To manage lung nodules, radiologists observe computed tomography images, review various imaging findings, and record these in radiology reports. The report contents should be of high quality and uniform regardless of the radiologist. Here, we propose an artificial intelligence system that automatically generates descriptions related to lung nodules in computed tomography images. Our system consists of an image recognition method for extracting contents-namely, bronchopulmonary segments and nodule characteristics from images-and a natural language processing method to generate fluent descriptions. To verify our system's clinical usefulness, we conducted an experiment in which two radiologists created nodule descriptions of findings using our system. Through our system, the similarity of the described contents between the two radiologists (p = 0.001) and the comprehensiveness of the contents (p = 0.025) improved, while the accuracy did not significantly deteriorate (p = 0.484).

Prevalence and clinical profiles of anti-myelin-associated glycoprotein neuropathy in Japan: A nationwide survey study of 133 patients.

BACKGROUND AND PURPOSE: The aim of this study was to determine the prevalence of anti-myelin-associated glycoprotein (MAG) neuropathy and the current status of such patients in Japan. METHODS: We conducted a nationwide survey in 2021 using established epidemiological methods. Questionnaires were sent to all neurology and pediatric neurology departments throughout Japan to identify patients with anti-MAG neuropathy. An initial questionnaire was used to determine the number of patients, with a second one used to collect detailed clinical information. RESULTS: The estimated number of patients with anti-MAG neuropathy was 353, with a prevalence of 0.28 per 100,000 and an incidence of 0.05 per 100,000. The detailed clinical profiles of 133 patients were available. The median (range) age of onset was 67 (30-87) years, with a prominent peak in the age range 66-70 years, and the male-to-female ratio was 3.6. Most patients had distal sensory-predominant polyneuropathy, and neuropathic pain (50%), or sensory ataxia (42%), while 18% had Waldenström's macroglobulinemia or multiple myeloma. Intravenous immunoglobulin was the most frequently used treatment (65%), but the response rate was <50%, whereas rituximab was given in 32% of patients, and 64% of these showed improvement. At the last visit, 27% of patients could not walk independently. CONCLUSIONS: This study on anti-MAG neuropathy provides updated insights into the epidemiology of this disease, clinical profiles, and treatment approaches in Japan. Rituximab therapy, used for only one-third of the patients, demonstrated efficacy. During the final visit, a quarter of the patients were unable to walk independently. Further studies are warranted to determine the optimal management of this rare and intractable disorder.

Prevalence, Clinical Profiles, and Prognosis of CIDP in Japanese Nationwide Survey: Analyses of 1,257 Diagnosis-Confirmed Patients.

BACKGROUND AND OBJECTIVES: To investigate the current epidemiology, clinical profile, and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) using a nationwide survey in Japan. METHODS: We conducted a nationwide survey using an epidemiologic method established in 2021. Questionnaire sheets were sent to the hospital departments of neurology and pediatric neurology throughout Japan. A primary questionnaire was used to determine the number of patients and their prevalence, and a second questionnaire was used to collect detailed clinical information. RESULTS: The primary survey showed that the estimated number of patients with CIDP was 4,180, with a prevalence of 3.3 per 100,000 persons. In the secondary survey, detailed clinical data were available for 1,257 patients. The male-to-female ratio was 1.5:1, and the median age at onset was 52 years. Typical CIDP was the most frequent subtype (52%), followed by distal (17%) and multifocal/focal CIDP (17%). Initial treatments included immunoglobulin therapy (72%), corticosteroids (15%), and others (13%). Among patients with CIDP, 78% had a progressive/relapsing course, 14% did not respond to first-line treatments, and 18% could not walk independently at the last visit. Among the subtypes, typical CIDP had the most severe disability before treatment (44% of patients could not walk independently). However, they showed a more favorable response to treatment than those with distal or multifocal CIDP. In the subgroup analyses, logistic regression analyses showed that younger age at onset, no muscle atrophy, and abnormal median-normal sural sensory nerve responses were associated with a higher probability of independent walking. DISCUSSION: Our study represents the largest cohort study on CIDP to demonstrate the current epidemiologic and clinical status of CIDP in Japan. Clinical subtypes seem to be associated with different treatment responses and outcomes; therefore, an appropriate treatment strategy according to the pathophysiology of each subtype is required to improve the prognosis of CIDP.

Diagnostic utility of Gold Coast criteria for amyotrophic lateral sclerosis in Asia.

Objective: This study aimed to reveal the diagnostic utility of Gold Coast (GC) criteria in Japanese patients with amyotrophic lateral sclerosis (ALS) by comparing the sensitivity/specificity with revised El Escorial (R-EE) and Awaji criteria, because its utility has not been studied in Asian ALS. Methods: Consecutive 639 patients (529 with ALS and 110 with ALS mimics), who were suspected of ALS and referred to three Japanese ALS centers, were enrolled. Diagnostic accuracy and characteristics of false positive and negative in GC criteria were compared with those of the Awaji and R-EE criteria. Patients were categorized as definite, probable or possible ALS according to each criterion. Results: The sensitivity of GC criteria (96.8%, 95% confidence interval [CI]: 95.3-98.3%) was higher than that of Awaji (89.6%, 95% CI: 87.0-92.2%) and R-EEC (89.2, 95% CI: 86.6-91.8%) criteria (both, p < 0.001). The specificity was also higher with GC criteria (77.3%, 95% CI: 69.5-85.1%) than Awaji (65.5%, 95% CI: 56.6-74.4%) and R-EEC (66.4, 95% CI: 57.6-75.2%) criteria (both, p < 0.01). Using GC criteria, patients with cervical spondylosis and Parkinson's syndrome tended to be diagnosed with ALS (i.e. "false positive"). Additionally, ALS patients diagnosed only by GC criteria less frequently had upper motor neuron (UMN) signs, compared with the other two criteria. Conclusion: Gold Coast criteria improve diagnostic accuracy for ALS in an Asian population, especially in patients with subtle UMN signs.

Increase in the prevalence of follicular regulatory T cells correlates with clinical efficacy of sublingual immunotherapy with house dust mites.

BACKGROUND: Allergic rhinitis (AR) impairs quality of life and affects nearly 40% of the Japanese population. Sublingual immunotherapy (SLIT) is the disease-modifying treatment for AR, but requires the selection of a biomarker associate with clinical efficacy in patients with AR who are treated with SLIT. The present study sought to examine objective biomarkers used for assessing the clinical efficacy of SLIT. METHODS: The authors examined the effects of 1 year of SLIT treatment with house dust mites (HDMs) using peripheral blood mononuclear cells (PBMCs) and serum from patients with AR. The prevalences of follicular regulatory T (Tfr), type 2 follicular helper T (Tfh2), type 2 helper T (Th2), conventional regulatory T (Treg), and type 1 regulatory T (Tr1) cells were examined by flow cytometry. Serum concentrations of HDM-specific IgA, IgE, and IgG4 antibodies, and HDM-induced production of interleukin (IL) 5 and IL-10 from cultured PBMCs were evaluated by enzyme-linked immunosorbent assay. RESULTS: Following 1 year of SLIT, the prevalences of Tfr, conventional Treg, and Tr1 cells were significantly increased, whereas that of Th2 cells and Tfh2 cells were significantly decreased; the serum concentration of HDM-specific IgG4 was significantly increased; and HDM-induced production of IL-5 from PBMCs was significantly decreased, while that of IL-10 was significantly increased. The increase in the prevalence of Tfr cells after SLIT correlated positively with the improvement of clinical symptom scores. CONCLUSION: An increase in Tfr cells may play an important role in SLIT, and may be a useful indicator for the clinical efficacy of SLIT.

Measurement of solid size in early-stage lung adenocarcinoma by virtual 3D thin-section CT applied artificial intelligence.

An artificial intelligence (AI) system that reconstructs virtual 3D thin-section CT (TSCT) images from conventional CT images by applying deep learning was developed. The aim of this study was to investigate whether virtual and real TSCT could measure the solid size of early-stage lung adenocarcinoma. The pair of original thin-CT and simulated thick-CT from the training data with TSCT images (thickness, 0.5-1.0 mm) of 2700 pulmonary nodules were used to train the thin-CT generator in the generative adversarial network (GAN) framework and develop a virtual TSCT AI system. For validation, CT images of 93 stage 0-I lung adenocarcinomas were collected, and virtual TSCTs were reconstructed from conventional 5-mm thick-CT images using the AI system. Two radiologists measured and compared the solid size of tumors on conventional CT and virtual and real TSCT. The agreement between the two observers showed an almost perfect agreement on the virtual TSCT for solid size measurements (intraclass correlation coefficient = 0.967, P < 0.001, respectively). The virtual TSCT had a significantly stronger correlation than that of conventional CT (P = 0.003 and P = 0.001, respectively). The degree of agreement between the clinical T stage determined by virtual TSCT and the clinical T stage determined by real TSCT was excellent in both observers (k = 0.882 and k = 0.881, respectively). The AI system developed in this study was able to measure the solid size of early-stage lung adenocarcinoma on virtual TSCT as well as on real TSCT.

Global analyses and potential effects of extracellular vesicles on the establishment of conceptus implantation during the peri-implantation period.

Intrauterine extracellular vesicles (EVs) are involved in establishing proper conceptus-endometrial communication, which is essential for conceptus implantation and subsequent successful placentation. Despite several studies on intrauterine EVs, the composition and quantitative changes in conceptus and endometrial EVs, as well as the effects of intrauterine EVs on endometrial epithelial cells (EECs) during the peri-implantation period, have not been well characterized. To elucidate global changes in proteins in EVs extracted from uterine flushings (UFs) during the pre-implantation (P17), just-implantation (P20), and post-implantation (P22) periods, the datasets of the proteome iTRAQ analysis were compared among P17, P20, and P22 EVs. These analyses revealed that the composition and function of proteins in the EVs changed dramatically during peri-implantation in cattle. Notably, intrauterine P17 EVs affected the high expression of "Developmental Biology" and "morphogenesis of an endothelium" compared with those in P20 and P22 EVs. Furthermore, P20 EVs had the functions of the high expression of "mitochondrial calcium ion homeostasis" and "Viral mRNA Translation" compared with those in P17 EVs. Transcripts extracted from EECs treated with P17, P20, or P22 EVs were subjected to RNA-seq analysis. These analyses identified 60 transcripts in EECs commonly induced by intrauterine EVs recovered from P17, P20, and P22, a large number of which were associated with "type I interferon signaling pathway". Collectively, these findings reveal the presence and multiple functions of EVs that are potentially implicated in facilitating conceptus implantation into the uterine epithelium during the peri-implantation period.

Sclerostin deficiency effectively promotes bone morphogenetic protein-2-induced ectopic bone formation.

BACKGROUND AND OBJECTIVE: Severe periodontitis causes alveolar bone resorption, resulting in tooth loss. Developments of tissue regeneration therapy that can restore alveolar bone mass are desired for periodontal disease. The application of bone morphogenetic protein-2 (BMP-2) has been attempted for bone fractures and severe alveolar bone loss. BMP-2 reportedly induces sclerostin expression, an inhibitor of Wnt signals, that attenuates bone acquisition. However, the effect of sclerostin-deficiency on BMP-2-induced bone regeneration has not been fully elucidated. We investigated BMP-2-induced ectopic bones in Sost-knockout (KO) mice. METHODS: rhBMP-2 were implanted into the thighs of C57BL/6 (WT) and Sost-KO male mice at 8 weeks of age. The BMP-2-induced ectopic bones in these mice were examined on days 14 and 28 after implantation. RESULTS: Immunohistochemical and quantitative RT-PCR analyses showed that BMP-2-induced ectopic bones expressed sclerostin in osteocytes on days 14 and 28 after implantation in Sost-Green reporter mice. Micro-computed tomography analysis revealed that BMP-2-induced ectopic bones in Sost-KO mice showed a significant increased relative bone volume and bone mineral density (WT = 468 mg/cm3 , Sost-KO = 602 mg/cm3 ) compared with those in WT mice on day 14 after implantation. BMP-2-induced ectopic bones in Sost-KO mice showed an increased horizontal cross-sectional bone area on day 28 after implantation. Immunohistochemical staining showed that BMP-2-induced ectopic bones in Sost-KO mice had an increased number of osteoblasts with osterix-positive nuclei compared with those in WT mice on days 14 and 28 after implantation. CONCLUSION: Sclerostin deficiency increased bone mineral density in BMP-2-induced ectopic bones.

Multiple quantum interrogation to determine the position of an object in a serial array of ring resonators.

We propose quantum interaction-free measurements to determine not only whether an object exists, but also where it is situated among possible interrogation positions. In the first configuration, the object exists at one of several possible positions, and the other positions are empty. We regard this as multiple quantum trap interrogation. In the second configuration, the object does not exist in any possible interrogation position, but other positions are occupied by objects. We refer to this as multiple quantum loophole interrogation. It is possible to determine the position of a trap or loophole with almost 100% certainty, without any real interaction between the photon and the objects. We performed a preliminary experiment using a serial array of add-drop ring resonators and confirmed that multiple trap and loophole interrogations are possible. We discuss the detuning of resonators from the critical coupling condition, the loss effects in the resonator, the frequency detuning effect of incident light, and the effect of object semitransparency on the interrogation systems.

A decreased prevalence of group 2 innate lymphoid cells in blood is associated with good postoperative outcomes in patients with chronic rhinosinusitis.

OBJECTIVE: Due to the high postoperative recurrence rate in eosinophilic chronic rhinosinusitis (eCRS) patients, there is a need for an index to predict the postoperative outcomes. Group 2 innate lymphoid cells (ILC2s) are important effector cells for type 2 immune responses in eosinophilic airway inflammation. The aim of this study was to investigate whether the prevalence of ILC2s in sinonasal tissues or in peripheral blood is associated with the postoperative outcome in CRS patients. METHODS: Twelve patients with eCRS and ten patients with non-eCRS were recruited. We examined the ILC2 prevalence in sinonasal tissues and in peripheral blood before and after endoscopic sinus surgery (ESS). Pre- and postoperative blood eosinophil counts were also examined. Lund-Mackay computed tomography (LMK-CT) scores were used to evaluate the disease severities and the postoperative outcomes; cases with more than 50% improvement were categorized into the good outcome group, and cases with less than 50% improvement were categorized into the poor outcome group. RESULTS: The ILC2 prevalence in sinonasal tissues was correlated with that in preoperative blood in eCRS and non-eCRS patients. The ILC2 prevalence in sinonasal tissues and in preoperative blood was not correlated with the pre- or postoperative LMK-CT scores. Postoperatively, the ILC2 prevalence in blood was decreased in eCRS and non-eCRS patients, and blood eosinophil count was also decreased in eCRS patients but not in non-eCRS patients. The ILC2 prevalence in postoperative blood was decreased in the good outcome group but not in the poor outcome group. Blood eosinophil counts were not decreased postoperatively in both good and poor outcome groups. CONCLUSION: The decreased ILC2 prevalence in postoperative blood may be a predictive biomarker for evaluating postoperative outcomes in eCRS and non-eCRS patients.

Fish and macroinvertebrate assemblages reveal extensive degradation of the world's rivers.

Rivers suffer from multiple stressors acting simultaneously on their biota, but the consequences are poorly quantified at the global scale. We evaluated the biological condition of rivers globally, including the largest proportion of countries from the Global South published to date. We gathered macroinvertebrate- and fish-based assessments from 72,275 and 37,676 sites, respectively, from 64 study regions across six continents and 45 nations. Because assessments were based on differing methods, different systems were consolidated into a 3-class system: Good, Impaired, or Severely Impaired, following common guidelines. The proportion of sites in each class by study area was calculated and each region was assigned a Köppen-Geiger climate type, Human Footprint score (addressing landscape alterations), Human Development Index (HDI) score (addressing social welfare), % rivers with good ambient water quality, % protected freshwater key biodiversity areas; and % of forest area net change rate. We found that 50% of macroinvertebrate sites and 42% of fish sites were in Good condition, whereas 21% and 29% were Severely Impaired, respectively. The poorest biological conditions occurred in Arid and Equatorial climates and the best conditions occurred in Snow climates. Severely Impaired conditions were associated (Pearson correlation coefficient) with higher HDI scores, poorer physico-chemical water quality, and lower proportions of protected freshwater areas. Good biological conditions were associated with good water quality and increased forested areas. It is essential to implement statutory bioassessment programs in Asian, African, and South American countries, and continue them in Oceania, Europe, and North America. There is a need to invest in assessments based on fish, as there is less information globally and fish were strong indicators of degradation. Our study highlights a need to increase the extent and number of protected river catchments, preserve and restore natural forested areas in the catchments, treat wastewater discharges, and improve river connectivity.

Changes in Gloss Alteration, Surface Roughness, and Color of Direct Dental Restorative Materials after Professional Dental Prophylaxis.

In the context of optimizing dental care for patients who are elderly, the purpose of this in vitro study was to evaluate the surface gloss (with a micro-area gloss meter) of, surface roughness (with a compact surface roughness measuring instrument) of, and color change (with a dental colorimeter) in two commercially available injectable resin-based composites (Estelite Universal Flow (EUF) and Beautifil Flow Plus F00 (BFP)) as well as two glass-ionomer cements (GC Fuji II LC CAPSULE (FLC) and GC Fuji IX GP EXTRA CAPSULE (FGP)), before and after dental prophylaxis. After 24 h, the surfaces of each specimen were polished at 2500 rpm with a prophy brush (Mersage Brush, Shofu) and one-step prophylaxis paste (Prophy Paste Pro, Directa): under 100 or 300 gf load, and for 10 or 30 s, 4× cycles of cleaning. After mechanical cleaning, conditions were found for a significant reduction in the gloss level (EUF, BFP, or FLC; p < 0.05) and a significant increase in surface roughness (BFP; 300 gf load, 10 s × four cycles of cleaning). Overall, the longer time or higher prophylaxis load tended to decrease the surface gloss. However, the observed change in surface roughness varied between the restorative materials. There was no color change post-prophylaxis.

Development and performance evaluation of a deep learning lung nodule detection system.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths throughout the world. Chest computed tomography (CT) is now widely used in the screening and diagnosis of lung cancer due to its effectiveness. Radiologists must identify each small nodule shadow from 3D volume images, which is very burdensome and often results in missed nodules. To address these challenges, we developed a computer-aided detection (CAD) system that automatically detects lung nodules in CT images. METHODS: A total of 1997 chest CT scans were collected for algorithm development. The algorithm was designed using deep learning technology. In addition to evaluating detection performance on various public datasets, its robustness to changes in radiation dose was assessed by a phantom study. To investigate the clinical usefulness of the CAD system, a reader study was conducted with 10 doctors, including inexperienced and expert readers. This study investigated whether the use of the CAD as a second reader could prevent nodular lesions in lungs that require follow-up examinations from being overlooked. Analysis was performed using the Jackknife Free-Response Receiver-Operating Characteristic (JAFROC). RESULTS: The CAD system achieved sensitivity of 0.98/0.96 at 3.1/7.25 false positives per case on two public datasets. Sensitivity did not change within the range of practical doses for a study using a phantom. A second reader study showed that the use of this system significantly improved the detection ability of nodules that could be picked up clinically (p = 0.026). CONCLUSIONS: We developed a deep learning-based CAD system that is robust to imaging conditions. Using this system as a second reader increased detection performance.

Combined Therapy with Ixazomib, Lenalidomide, and Dexamethasone for Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes Syndrome.

Objective Immunomodulatory drugs and proteasome inhibitors are therapeutic options for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. This study aimed to evaluate the efficacy and safety of the combination of ixazomib, lenalidomide, and dexamethasone (IRd) for POEMS syndrome. Methods Six consecutive patients with POEMS syndrome who were treated with the IRd regimen at Chiba University Hospital between April 2018 and August 2021 were included. Serum M-protein and serum vascular endothelial growth factor (sVEGF) levels, overall neuropathy limitation scales (ONLS), clinical symptoms, and adverse events were assessed. Results Of the six patients, five had received prior treatments. Patients received a median of 5 cycles (range, 3-28 cycles) of IRd. Following treatment, serum M-protein disappeared in two patients, sVEGF levels returned to normal in two patients, two patients showed a reduction in the ONLS of 1, and clinical symptoms improved in four patients. The median level of sVEGF decreased from 2,395 pg/mL (range, 802-6,120 pg/mL) to 1,428 pg/mL (range, 183-3,680 pg/mL) in three months. Adverse events, including rash, neutropenia, sensory peripheral neuropathy, and nausea, were observed in three patients, which necessitated dose reduction or discontinuation of treatment. Conclusion IRd can be a therapeutic option for POEMS syndrome, albeit with careful monitoring of adverse events.

Relationship between motor cortical and peripheral axonal hyperexcitability in amyotrophic lateral sclerosis.

BACKGROUND: Previous studies have shown that patients with amyotrophic lateral sclerosis (ALS) have hyperexcitability in both the motor cortex and peripheral motor axons, but the relationship between central and peripheral excitability has not been fully disclosed. METHODS: Threshold tracking transcranial magnetic stimulation (TMS) and motor nerve excitability testing were prospectively performed in 53 patients with ALS and 50 healthy subjects, and their relations to compound muscle action potential (CMAP) amplitude and revised ALS Functional Rating Scale were cross-sectionally analysed. RESULTS: Compared with controls, patients with ALS showed both cortical and peripheral hyperexcitability; TMS showed reduced short-interval intracortical inhibition (interstimulus interval 1-7 ms) (p<0.001) and shortened silent period (p<0.05), and median nerve excitability testing revealed greater changes in depolarising threshold electrotonus (TEd) and greater superexcitability (p<0.0001, both), suggesting reduced axonal potassium currents. Significant correlations between cortical and peripheral excitability indices were not found. Greater changes in TEd (90-100 ms) (R=-0.33, p=0.03) and superexcitability (R=0.36, p=0.01) were associated with smaller amplitude of CMAP, whereas cortical excitability indices had no correlation with CMAP amplitude. More rapid motor functional decline was associated with only greater TEd (90-100 ms) (ß=0.46, p=0.001). CONCLUSIONS: Our results suggest that in ALS, cortical excitability is continuously high regardless of the extent of the peripheral burden, but peripheral hyperexcitability is associated with the extent of the peripheral burden and disease evolution speed. Alterations of ion channel function may play an important role in ALS pathophysiology.

A Histochemical Analysis of Neurofibrillary Tangles in Olfactory Epithelium, a Study Based on an Autopsy Case of Juvenile Alzheimer's Disease.

The pathological changes of Alzheimer's disease (AD) begin 10-20 years before clinical onset, and it is therefore desirable to identify effective methods for early diagnosis. The nasal mucosa is a target tissue for measuring AD-related biomarkers because the olfactory nerve is the only cranial nerve that is exposed to the external environment. We describe an autopsy case of rapidly advanced juvenile AD (JAD), focusing on the olfactory system. The formation of senile plaques, neurofibrillary tangles (NFTs), and neuropil threads was examined in the temporal cortex, hippocampus, olfactory bulb, and olfactory and respiratory epithelia in the bilateral olfactory clefts. Neurodegenerative changes in the olfactory and respiratory epithelia and the pathological deposition of amyloid ß42 (Aß42) and phosphorylated tau were also examined. As a result, senile plaques, NFTs, and neuropil threads were found in the temporal cortex, hippocampus, and olfactory bulb. NFTs were also found in the olfactory epithelium. Degenerated olfactory cells and their axons stained positive for phosphorylated tau. Supporting cells in the degenerated olfactory epithelium stained positive for Aß42. In conclusion, pathological biomarkers of AD were expressed in the degenerated olfactory epithelium of this JAD patient. This observation suggests that nasal samples may be useful for the diagnosis of AD.