High levels of plasma neurofilament light chain correlated with brainstem and peripheral nerve damage.

Background And Objectives: Blood neurofilament light chain (NfL) is a minimally invasive, but highly sensitive biomarker of neurological diseases. However, diseases and neurological damage associated with increased NfL remain unclear. Therefore, the present study investigated factors associated with increased plasma NfL levels in various neurological diseases, focal lesions and pathological processes.

Clinical Evaluation of Cerebrospinal Fluid p217tau and Neurofilament Light Chain Levels in Patients with Alzheimer's Disease or Other Neurological Diseases.

Background: The cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 217 (p217tau) or 181 (p181tau), and neurofilament light chain (NfL) are definite biomarkers of tauopathy and neurodegeneration in Alzheimer's disease (AD).

Objective: To validate their utility in excluding other neurological diseases and age-related changes in clinical settings.

Methods: We developed monoclonal antibodies against p217tau and NfL, established novel ELISAs, and analyzed 170 CSF samples from patients with AD or other neurological diseases.

Annual stability of the plasma Aß40/42 ratio and associated factors.

Objective: The plasma Aß40/42 ratio is a biomarker of brain amyloidosis. However, the threshold difference between amyloid positivity and negativity is only 10-20% and fluctuates with circadian rhythms, aging, and APOE-ε4 during the decades of evolution of Alzheimer's disease.

Methods: Plasma Aß40 and Aß42 levels in 1472 participants aged between 19 and 93 years in the Iwaki Health Promotion Project for 4 years were statistically analyzed.

Plasma ApoE4 Levels Are Lower than ApoE2 and ApoE3 Levels, and Not Associated with Plasma Aβ40/42 Ratio as a Biomarker of Amyloid-β Amyloidosis in Alzheimer's Disease.

Background: APOE4 is the strongest risk factor for Alzheimer's disease (AD). However, limited information is currently available on APOE4 and the pathological role of plasma apolipoprotein E (ApoE) 4 remains unclear.

Objective: The aims of the present study were to measure plasma levels of total ApoE (tE), ApoE2, ApoE3, and ApoE4 using mass spectrometry and elucidate the relationships between plasma ApoE and blood test items.

Lipid Rafts Act as a Common Platform for Amyloid-β Oligomer-Induced Alzheimer's Disease Pathology.

Background: Amyloid-β (Aβ) oligomers induce the overproduction of phosphorylated tau and neurodegeneration. These cascades gradually cause cognitive impairment in Alzheimer's disease (AD). While each pathological event in AD has been studied in detail separately, the spatial and temporal relationships between pathological events in AD remain unclear.

Age-Related Cognitive Decline and Prevalence of Mild Cognitive Impairment in the Iwaki Health Promotion Project.

Background: The Iwaki Health Promotion Project (IHPP) is a community-based study for the prevention of lifestyle-related diseases and improvement of quality of life.

Objective: Between 2014 and 2017, a total of 4,442 Iwaki town residents from 19 to 93 years of age participated in annual surveys to clarify the natural course of age-related cognitive decline and mild cognitive impairment (MCI).

Methods: Modified OLD and SED-11Q questionnaires, MMSE, Logical Memory II, educational history, and APOE genotypes were examined at the first screening.

IgG4-related hypothalamo-hypophysitis.

•A patient exhibited IgG4-related hypothalamo-hypophysitis.•Prominent high-signal areas of swelling were observed in the hypothalamus, tuber cinereum, infundibulum, and bilateral optic nerve systems.•MRI T1WI with contrast media demonstrated enhanced neurohypophysis and cystic swelling, and compressed anterior pituitary.

Quantitative Measurement of Cerebrospinal Fluid Amyloid-β Species by Mass Spectrometry.

Background: High sensitivity liquid chromatography mass spectrometry (LC-MS/MS) was recently introduced to measure amyloid-β (Aβ) species, allowing for a simultaneous assay that is superior to ELISA, which requires more assay steps with multiple antibodies.

Objective: We validated the Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 assay by LC-MS/MS and compared it with ELISA using cerebrospinal fluid (CSF) samples to investigate its feasibility for clinical application.

Methods: CSF samples from 120 subjects [8 Alzheimer's disease (AD) with dementia (ADD), 2 mild cognitive dementia due to Alzheimer's disease (ADMCI), 14 cognitively unimpaired (CU), and 96 neurological disease subjects] were analyzed.

Improved Neuroimaging Findings and Cognitive Function in a Case of High-altitude Cerebral Edema.

High-altitude cerebral edema (HACE) is a rare condition of acute mountain sickness that manifests as consciousness disturbance and truncal ataxia. Neuroimaging shows vasogenic edema with microbleeds in the white matter and the corpus callosum. We herein report a case of HACE in which the patient showed widespread hyperintense signals with extensive microbleeds in the white matter and corpus callosum on MRI, as well as cognitive dysfunction.

Successful basilar artery dilatation in pure bilateral cerebral peduncular infarctions using balloon angioplasty.

•An extremely rare case of bilateral cerebral peduncular infarctions (BCPI) is reported.•The detection of the pure Mickey Mouse ears sign on MRI is an indicator of a need for reperfusion therapy.•Severe stenosis of the basilar artery (BA) and a poor collateral supply from both posterior cerebral arteries were seen.

Spastic Paraplegia with Paget's Disease of Bone due to a VCP Gene Mutation.

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder clinically characterized by slowly progressing spastic paraparesis. We herein report a 50-year-old Japanese woman who presented with slowly progressing spastic paraplegia and a history of Paget's disease of bone (PDB). Genetic testing revealed a mutation of the Valosin-containing protein (VCP) gene (p.

Novel ELISAs to measure total and phosphorylated tau in cerebrospinal fluid.

Cerebrospinal fluid (CSF) total tau (t-tau) and tau protein phosphorylated at threonine 181 (p181tau) are established biomarkers for Alzheimer's disease (AD). Herein, we measured t-tau and p181tau to evaluate novel enzyme-linked immunosorbent assays (ELISAs) using 72 CSF samples including from patients with AD with dementia (ADD) and various neurodegenerative diseases. Our assay system showed good correlations with widely used ELISA systems for t-tau and p181tau and showed that serum and hemoglobin contamination in CSF samples did not decrease sensitivity.

CogEvo, a cognitive function balancer, is a sensitive and easy psychiatric test battery for age-related cognitive decline.

Aim: We examined whether a newly developed computer-aided neuropsychiatric series of test, CogEvo, is necessary and sufficient for the evaluation of cognitive function in older people.

Methods: A total of 272 participants in worthwhile life activity for the prevention of decline in mobility and cognitive function were administered tests every week at 33 locations in Fukaura-machi, Japan. Basic profile information, a Mini-Mental State Examination (MMSE), a CogEvo and a clock drawing test were used in the present study.

Perineuritis Successfully Treated with Early Aggressive Immunotherapy.

Perineuritis is a rare type of peripheral neuropathy defined by swelling and cellular infiltration in the perineurium. We herein report a 52-year-old man who presented with subacute onset pain from the back to the lower limbs, muscle weakness and hypoesthesia. A sural nerve biopsy revealed perineuritis, consisting of inflammatory cell infiltration and swelling of the perineurium.

Oral Immunization with Soybean Storage Protein Containing Amyloid-β 4-10 Prevents Spatial Learning Decline.

Amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Because AD pathologies begin two decades before the onset of dementia, prevention of Aβ amyloidosis has been proposed as a mean to block the pathological cascade. Here, we generate a transgenic plant-based vaccine, a soybean storage protein containing Aβ4-10, named Aβ+, for oral Aβ immunization.

Cerebrospinal Fluid and Plasma Biomarkers in Neurodegenerative Diseases.

Cerebrospinal fluid (CSF) amyloid-β (Aβ)42 and tau are biomarkers for Alzheimer's disease (AD); however, the effects of other neurodegenerative processes on these biomarkers remain unclear. We measured Aβ40, Aβ42, total tau, phosphorylated-tau, and α-synuclein in CSF and plasma using matched samples from various neurodegenerative diseases to expand our basic knowledge on these biomarkers and their practical applications. A total of 213 CSF and 183 plasma samples were analyzed from cognitively unimpaired subjects, and patients with Alzheimer's disease dementia (ADD), mild cognitive impairment (MCI), non-AD dementias, and other neurological diseases.

Severe Chronic Inflammatory Demyelinating Polyneuropathy Ameliorated following High-dose (3 g/kg) Intravenous Immunoglobulin Therapy.

We report the case of a 53-year-old woman with severe chronic inflammatory demyelinating polyneuropathy (CIDP) who developed progressive tetraplegia with respiratory failure despite receiving a standard dose of intravenous immunoglobulin therapy (IVIg), steroid pulse therapy, plasma exchange, and cyclosporine. We administered high-dose IVIg (3 g/kg; 0.6 g/kg/day for 5 consecutive days at monthly intervals).

Aging and are determinative factors of plasma A42 levels.

Objective: The aim of this study was to confirm determinative factors for plasma A and its association with cognitive function.

Methods: Fasting plasma A40 and A42 levels were measured by ELISA in 1019 participants in the Iwaki Health Promotion Project. The relationships between plasma A and health-related items, including physical characteristics, cognitive function tests, blood chemistry, and genotype were analyzed.

[A case of hereditary neuropathy with liability to pressure palsies due to push-up exercise].

A 17-year-old man with no familial history developed motor and sensory disturbance of the left upper limb a few days after starting push-up exercise. Neurological examination revealed broad weakness and radial sensory disturbance of the left upper limb and magnetic resonance neurography showed laterality of brachial plexus intensity signals. Therefore, we suspected left brachial plexopathy.

Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure.

Background: In hereditary myopathy with early respiratory failure (HMERF), cytoplasmic bodies (CBs) are often localised in subsarcolemmal regions, with necklace-like alignment (necklace CBs), in muscle fibres although their sensitivity and specificity are unknown.

Objective: To elucidate the diagnostic value of the necklace CBs in the pathological diagnosis of HMERF among myofibrillar myopathies (MFMs).

Methods: We sequenced the exon 343 of TTN gene (based on ENST00000589042), which encodes the fibronectin-3 (FN3) 119 domain of the A-band and is a mutational hot spot for HMERF, in genomic DNA from 187 patients from 175 unrelated families who were pathologically diagnosed as MFM.

Stable accumulation of seed storage proteins containing vaccine peptides in transgenic soybean seeds.

There has been a significant increase in the use of transgenic plants for the large-scale production of pharmaceuticals and industrial proteins. Here, we report the stable accumulation of seed storage proteins containing disease vaccine peptides in transgenic soybean seeds. To synthesize vaccine peptides in soybean seeds, we used seed storage proteins as a carrier and a soybean breeding line lacking major seed storage proteins as a host.