[65 years old man of chronic inflammatory demyelinating polyneuritis (CIDP) which presented radicular swelling and was able to confirm image progress before the onset].

The case is a 65 years old man. He noticed muscle weakness of lower limbs from 3 years ago. Dysesthesia was developed, He came in our hospital in X year. He was detected muscle weakness, sensory disturbance in distal lower limbs predominance and detected radicular significant swelling in spinal cord MRI and diagnosed it with chronic inflammatory demyelinating polyneuritis (CIDP). In the follow-up purpose of other diseases regularly, it was confirmed that nerve root was gradually swelling from around 7 years before the onset. The radicular swelling is one of the characteristics in CIDP, supports the diagnosis. This case was the valuable case that was able to chase image progress before the onset.

Augmenting Nesidiocoris tenuis (Nesidiocoris) with a Factitious Diet of Artemia Cysts to Control Bemisia tabaci (Gennadius) on Tomato Plants under Greenhouse Conditions.

Natural predators such as Nesidiocoris tenuis are known for their role in managing greenhouse pests. However, techniques in maximizing the biological control potential of N. tenuis under field conditions are still lacking. We evaluated under greenhouse conditions the prospects of Artemia cysts enhanced with high fructose corn syrup and honey, and delivered using hemp strings (hemp rope) as supplementary factitious dietary in augmenting the proliferation and spread of N. tenuis on tomato plants. Results showed that N. tenuis supplemented with hemp rope could establish, proliferate and disperse among tomato plants compared to the N. tenuis supplemented with banker plants. Even though N. tenuis proliferated exponentially on banker plants, their movement and relocation to tomato plants, as expected, were only congested on tomato plants near the banker plants. However, as the survey continued, they relocated to the rest of the tomato plants. Furthermore, the number of Bemisia tabaci eggs and nymphs, a serious greenhouse pest of tomato, was observed to be significantly reduced in hemp rope greenhouse compared to banker plants and the negative control (no pest control system) greenhouses. This study, therefore, establishes foundational data on the usage of Artemia cysts enhanced with isomerized sugar (high fructose corn syrup) and honey under greenhouse conditions as factitious supplementary dietary in supporting N. tenuis establishment and spread, traits that are essential towards development of whitefly Integrated Pest Management (IPM) system. enhanced with isomerized sugar (high fructose corn syrup) and honey.

Characteristic microglial features in patients with hereditary diffuse leukoencephalopathy with spheroids.

OBJECTIVE: To clarify the histopathological alterations of microglia in the brains of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) caused by mutations of the gene encoding the colony stimulating factor-1 receptor (CSF-1R). METHODS: We examined 5 autopsied brains and 1 biopsy specimen from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical, biochemical, and ultrastructural features of microglia were examined, and quantitative analyses were performed. RESULTS: In layers 3 to 4 of the frontal cortex in HDLS brains, microglia showed relatively uniform and delicate morphology, with thin and winding processes accompanying knotlike structures, and significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1-positive cells were evident in comparison with control brains. On the other hand, in layers 5 to 6 and the underlying white matter, microglia were distributed unevenly; that is, in some areas they had accumulated densely, whereas in others they were scattered. Immunoblot analyses of microglia-associated proteins, including CD11b and DAP12, revealed that HDLS brains had significantly lower amounts of these proteins than diseased controls, although Ki-67-positive proliferative microglia were not reduced. Ultrastructurally, the microglial cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic reticulum and disaggregated polyribosomes, indicating depression of protein synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or P2ry12, indicating that they were derived from bone marrow. INTERPRETATION: The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations. Ann Neurol 2016;80:554-565.

Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17.

Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri.niigata-u.ac.jp/.

ApoE-isoform-dependent cellular uptake of amyloid-ß is mediated by lipoprotein receptor LR11/SorLA.

The formation of senile plaques composed of ß-amyloid (Aß) in the brain is likely the initial event in Alzheimer's disease (AD). Possession of the APOE ε4 allele, the strong genetic factor for AD, facilitates the Aß deposition from the presymptomatic stage of AD in a gene-dosage-dependent manner. However, the precise mechanism by which apoE isoforms differentially induce the AD pathology is largely unknown. LR11/SorLA is a type I membrane protein that functions as the neuronal lipoprotein endocytic receptor of apoE and the sorting receptor of the amyloid precursor protein (APP) to regulate amyloidogenesis. Recently, LR11/SorLA has been reported to be involved in the lysosomal targeting of extracellular amyloid-ß (Aß) through the binding of Aß to the vacuolar protein sorting 10 (VPS10) protein domain of LR11/SorLA. Here, we attempted to examine the human-apoE-isoform-dependent effect on the cellular uptake of Aß through the formation of a complex between an apoE isoform and LR11/SorLA. Cell culture experiments using Neuro2a cells revealed that the cellular uptake of secreted apoE3 and apoE4 was enhanced by the overexpression of LR11/SorLA. In contrast, the cellular uptake of apoE2 was not affected by the expression of LR11/SorLA. Co-immunoprecipitation assay revealed that apoE-isoform-dependent differences were observed in the formation of an apoE-LR11 complex (apoE4>apoE3>apoE2). ApoE-isoform-dependent differences in cellular uptake of FAM-labeled Aß were further investigated by coculture assay in which donor cells secrete one of the apoE isoforms and recipient cells express FL-LR11. The cellular uptake of extracellular Aß into the recipient cells was most prominently accentuated when cocultured with the donor cells secreting apoE4 in the medium, followed by apoE3 and apoE2. Taken together, our results provide evidence for the mechanism whereby human-apoE-isoform-dependent differences modulate the cellular uptake of Aß mediated by LR11/SorLA.

Hyperphosphorylation of Tau induced by naturally secreted amyloid-ß at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3ß signaling pathway.

Alzheimer disease (AD) is neuropathologically characterized by the formation of senile plaques from amyloid-ß (Aß) and neurofibrillary tangles composed of phosphorylated Tau. Although there is growing evidence for the pathogenic role of soluble Aß species in AD, the major question of how Aß induces hyperphosphorylation of Tau remains unanswered. To address this question, we here developed a novel cell coculture system to assess the effect of extracellular Aß at physiologically relevant levels naturally secreted from donor cells on the phosphorylation of Tau in recipient cells. Using this assay, we demonstrated that physiologically relevant levels of secreted Aß are sufficient to cause hyperphosphorylation of Tau in recipient N2a cells expressing human Tau and in primary culture neurons. This hyperphosphorylation of Tau is inhibited by blocking Aß production in donor cells. The expression of familial AD-linked PSEN1 mutants and APP ΔE693 mutant that induce the production of oligomeric Aß in donor cells results in a similar hyperphosphorylation of Tau in recipient cells. The mechanism underlying the Aß-induced Tau hyperphosphorylation is mediated by the impaired insulin signal transduction because we demonstrated that the phosphorylation of Akt and GSK3ß upon insulin stimulation is less activated under this condition. Treating cells with the insulin-sensitizing drug rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, attenuates the Aß-dependent hyperphosphorylation of Tau. These findings suggest that the disturbed insulin signaling cascade may be implicated in the pathways through which soluble Aß induces Tau phosphorylation and further support the notion that correcting insulin signal dysregulation in AD may offer a potential therapeutic approach.