β-Amyloid peptide (1–40) in the brain reaches the nasal cavity via a non-blood pathway

Kameshima, Naoko; Yanagisawa, Daijiro; Tooyama, Ikuo

doi:10.1016/j.neures.2013.03.016

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…Ayala-Grosso et al reported that patient-derived olfactory stromal cells from biopsies of olfactory mucosa expressed Aβ peptides [ 23 ]. Our previous study using a rat model showed that Aβ peptides injected in the brain were transported from the brain into the nasal cavity [ 16 ]. The present study showed that the p-tau/t-tau ratio in the nasal cavity was significantly higher in AD cases than in controls, in the olfactory cleft and middle nasal meatus.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Aβ and tau deposits have been found in the olfactory epithelium of AD cases at autopsy [ 14, 15 ]. Animal experiments have shown that ventricle-injected isotope-labelled beta-amyloid peptide ( 125 I-Aβ40) is transported to the nasal cavity through a non-hematogenous pathway [ 16 ]. Deposits of Aβ peptides in the nasal mucosa in a transgenic mouse model of AD have been found to be well correlated with the amounts of Aβ depositions in the brain [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Development of a High-Sensitivity Method for the Measurement of Human Nasal Aβ42, Tau, and Phosphorylated Tau

Liu

Kameshima

Nanjo

et al. 2018

JAD

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Cost-effective and feasible methods for early diagnosis of Alzheimer’s disease (AD) are needed. We present two methods to measure AD-related biomarkers simultaneously from one nasal smear for the purpose of diagnosing AD. Japanese men and women aged 63–85 years old were recruited in 2015–2016 for this case–control study. A total of 25 AD cases and 25 controls (22 men and 28 women) participated in this research. Nasal smears were collected from the common nasal meatus, inferior concha, middle nasal meatus, and olfactory cleft, and the proteins in the samples were analyzed by two methods, which we named PGD (Pre-treatment with guanidine- n-Dodecyl-beta-D-maltoside solution) method 1 (PGD-I) and 2 (PGD-II). The PGD-I method measured total tau and amyloid-β (Aβ)42, but no differences in median levels of total tau and Aβ42 between AD cases and controls were found in any of the nasal locations. The PGD-II method measured Aβ42, total tau, and phosphorylated tau, but levels of Aβ40 in all nasal locations of both groups were near zero. Median levels of phosphorylated tau to total tau (p-tau/t-tau) ratios in the middle nasal meatus and in the olfactory cleft were significantly higher in AD cases than in controls, and could significantly predict AD. To assess diagnostic reliability, areas under the ROC curve were 0.74 (95% CL = 0.52–0.95, p = 0.030) for the middle nasal meatus and 0.72 (95% CL = 0.52–0.92, p = 0.029) for the olfactory cleft. Thus, PGD-I and PGD-II can detect AD-related biomarkers in nasal smears and PGD-II may be a useful tool for diagnosing AD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a High-Sensitivity Method for the Measurement of Human Nasal Aβ42, Tau, and Phosphorylated Tau

Liu

Kameshima

Nanjo

et al. 2018

JAD

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“…It has been reported that in AβPP/PS1 transgenic mice, the deposition of Aβ began in the olfactory system and then spread to the hippocampus and cortex 21 . In experiments in rats, ventricle-injected isotope-labelled Aβ peptide ( 125 I-Aβ40) was shown to be transported to the nasal cavity through a non-haematogenous pathway 22 . In another recent study, median levels of p-tau/t-tau ratios in the middle nasal meatus and in the olfactory cleft were significantly higher in AD cases than in controls, but the levels of Aβ 42 and Aβ 40 were near zero and were not different between AD cases and controls 23 .…”

Section: Introductionmentioning

confidence: 99%

Amyloid beta in nasal secretions may be a potential biomarker of Alzheimer’s disease

Kim

Lee

Cho

et al. 2019

Sci Rep

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We investigated the level of amyloid beta (Aβ) in nasal secretions of patients with Alzheimer’s disease dementia (ADD) using interdigitated microelectrode (IME) biosensors and determined the predictive value of Aβ in nasal secretions for ADD diagnosis. Nasal secretions were obtained from 35 patients with ADD, 18 with cognitive decline associated with other neurological disorders (OND), and 26 cognitively unimpaired (CU) participants. Capacitance changes in IMEs were measured by capturing total Aβ (ΔCtAβ). After 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) was injected, additional capacitance changes due to the smaller molecular weight Aβ oligomers disassembled from the higher molecular weight oligomeric Aβ were determined (ΔCoAβ). By dividing two values, the capacitance ratio (ΔCoAβ/ΔCtAβ) was determined and then normalized to the capacitance change index (CCI). The CCI was higher in the ADD group than in the OND (p = 0.040) and CU groups (p = 0.007). The accuracy of the CCI was fair in separating into the ADD and CU groups (area under the receiver operating characteristic curve = 0.718, 95% confidence interval = 0.591–0.845). These results demonstrate that the level of Aβ in nasal secretions increases in ADD and the detection of Aβ in nasal secretions using IME biosensors may be possible in predicting ADD.

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“…In APP/presenilin (PS1) transgenic mice, the deposition of Aβ began in the olfactory system and then spread to the brain [ 45 ]. Moreover, when an isotope-labeled Aβ peptide was injected into the ventricle of an experimental rat, it was observed that the Aβ peptide was transported from the brain to the nasal cavity through a nonhematogenous pathway [ 46 ]. Interestingly, Kim et al demonstrated that the Aβ levels in nasal secretions was higher in AD patients than in individuals without cognitive impairment [ 47 ], suggesting that the detection of Aβ in nasal secretions may be a potential biomarker for predicting AD.…”

Section: Discussionmentioning

confidence: 99%

Human Palatine Tonsils Are Linked to Alzheimer’s Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection

Lim

Lee

Kim

et al. 2022

Cells

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Amyloid-β (Aβ)-peptide production or deposition in the neuropathology of Alzheimer’s disease (AD) was shown to be caused by chronic inflammation that may be induced by infection, but the role of pathogenic-bacteria-related AD-associated Aβ is not yet clearly understood. In this study, we validated the hypothesis that there is a correlation between the Aβ-protein road and bacterial infection and that there are effects of bacteria, Staphylococcus aureus (S. aureus), on the Aβ road in the inflammatory environment of human tonsils. Here, we detected Aβ-peptide deposits in human tonsil tissue as well as tissue similar to tonsilloliths found in the olfactory cleft. Interestingly, we demonstrated for the first time the presence of Staphylococcus aureus (S. aureus) clustered around or embedded in the Aβ deposits. Notably, we showed that treatment with S. aureus upregulated the Aβ-protein road in cultures of human tonsil organoids and brain organoids, showing the new role of S. aureus in Aβ-protein aggregation. These findings suggest that a reservoir of Aβ and pathogenic bacteria may be a possible therapeutic target in human tonsils, supporting the treatment of antibiotics to prevent the deposition of Aβ peptides via the removal of pathogens in the intervention of AD pathogenesis.

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β-Amyloid peptide (1–40) in the brain reaches the nasal cavity via a non-blood pathway

Cited by 8 publications

References 19 publications

Development of a High-Sensitivity Method for the Measurement of Human Nasal Aβ42, Tau, and Phosphorylated Tau

Development of a High-Sensitivity Method for the Measurement of Human Nasal Aβ42, Tau, and Phosphorylated Tau

Amyloid beta in nasal secretions may be a potential biomarker of Alzheimer’s disease

Human Palatine Tonsils Are Linked to Alzheimer’s Disease through Function of Reservoir of Amyloid Beta Protein Associated with Bacterial Infection

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