Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of beta-amyloid oligomer

Olfactory dysfunction is a common symptom associated with neurodegenerative diseases including Alzheimer's disease (AD). Although evidence exists to suggest that peripheral olfactory organs are involved in the olfactory dysfunction that accompanies AD pathology, the underlying mechanisms are not fully understood. As confirmed using behavioral tests, transgenic mice overexpressing a Swedish mutant form of human amyloid precursor proteins exhibited olfactory impairments prior to evidence of cognitive impairment. By measuring the expression of tyrosine hydroxylase, we observed that specific regions of the olfactory bulb (OB) in Tg2576 mice, specifically the ventral portion exhibited significant decreases in the number of dopaminergic neurons in the periglomerular regions from the early stage of AD. To confirm the direct linkage between these olfactory impairments and AD-related pathology, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-the initiating enzyme in A beta genesis-and beta-amyloid peptide (A beta), hallmarks of AD were analyzed. We found that an increase in BACE1 expression coincided with an elevation of amyloid-beta (A beta) oligomers in the ventral region of OB. Moreover, olfactory epithelium (OE), in particular the ectoturbinate in which axons of olfactory sensory neurons (OSNs) have direct connections with the dendrites of mitral/tufted cells in the ventral part of OB, exhibited significant decreases in both thickness and cell number even at early stages. This result suggests that A beta oligomer toxicity in the OE may have induced a decline in the number of OSNs and functional impairment of the olfactory system. We first demonstrated that disproportionate levels of regional damage in the peripheral olfactory system may be a specific symptom of AD with A beta oligomer accumulation occurring prior to damage within the CNS. This regional damage in the olfactory system early in the progression of AD may be closely related to AD-related pathological abnormality and olfactory dysfunction found in AD patients.1

A Capsule-Type Microrobot with Pick-and-Drop Motion for Targeted Drug and Cell Delivery

A capsule-type microrobot exhibits pick-and-drop (P&D) motion to hold a particle within a confined volume and transports it via a corkscrewing motion. The P&D motion is possible because the capsule-type microrobot has two parts: a plunger and a cap. The fabricated microrobots are wirelessly controlled by a magnetic manipulator. Drugs or cells can be encapsulated in the container of the capsule-type microrobot by the P&D motion or attached to the surface of the cap, which can be used as a supporting structure. Therefore, the capsule-type microrobot can deliver suspended or adherent cells. The drug or cells are minimally exposed or not completely exposed to the surrounding fluid and do not experience shear force when encapsulated in the container. As a proof-of-concept, secure transportation of microparticles in the confined volume of the capsule via P&D motion is demonstrated. In addition, the cap is used as a scaffold for neuronal cell culture on a rat brain slice to demonstrate its biocompatibility and feasibility for targeted cell delivery. The proposed capsule-type microrobot is suitable for diverse applications, as it protects the encapsulated materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.1

Plasma soluble neuregulin-1 as a diagnostic biomarker for Alzheimer's disease

To identify some apparent biomarker candidates for the diagnosis of Alzheimer's disease (AD) pathology, we investigated whether there would be a significant difference between the levels of the plasma proteins of AD patients and healthy people. A total of 115 subjects were enrolled, 60 individuals with AD and 55 healthy controls. There was a statistical difference in the mini-mental status exam (MMSE) scores and the clinical dementia rating (CDR) scores between the two groups. We used the immunoblotting assay to analyze several plasma proteins in the subjects. Amyloid-β (Aβ), S100a9, and soluble neuregulin-1 (sNRG-1), including α-synuclein (α-Syn) as a detection control were detected in the plasma samples. Unlike Aβ, S100a9 and α-Syn, the level of sNRG-1 of the AD patients was significantly higher than that of the healthy control subjects. The AD patients were divided into mild and moderate groups according to their MMSE and CDR scores. We found a significant correlation between the level of sNRG-1 and MMSE scores. The sNRG-1 level was significantly higher in mild AD patients as well as in moderate AD patients compared with that of the control subjects. These new findings indicate that increased plasma sNRG-1 levels might be a novel and reliable biological marker for the early diagnosis of AD. © 2016 Elsevier Ltd. All rights reserved.1

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present