Evaluation of [F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies.

Tau aggregates represent a key pathologic feature of Alzheimer's disease and other neurodegenerative diseases. Recently, PET probes have been developed for detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer's disease tauopathies. The novel tau PET tracer, [F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer's disease and non-Alzheimer's disease tauopathies.

Multiple Cerebral Infarctions Accompanied by Subcortical and Subarachnoid Hemorrhaging in Bilateral Border Zone Areas in a Patient with Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with peripheral neuropathy, but reports of central nervous system involvement are quite rare. We herein report a patient with EGPA first identified as having hypereosinophilia who later developed asthma, eosinophilic otitis media, sinusitis, and hemorrhagic colitis. She subsequently developed hemiparesis.

Electroconvulsive Therapy for Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: Electroconvulsive therapy (ECT) is a well-established treatment for psychiatric disorders, including depression and psychosis. ECT has been reported to be effective in treating such psychiatric symptoms in patients with Parkinson's disease (PD) and has been also reported to be effective in treating motor symptoms. The aim of the study is to summarize previous clinical studies investigating the efficacy of ECT for symptoms in patients with PD.

The utility of simple questions to evaluate cognitive impairment.

Objectives: As the population of patients with cognitive decline grows, physicians and caregivers need brief screening tools. Comprehensive neurocognitive batteries require special training and time for evaluation. We focused on accessibility and compared the diagnostic power of several easy questions.

Disclosure of Amyloid Status for Risk of Alzheimer Disease to Cognitively Normal Research Participants With Subjective Cognitive Decline: A Longitudinal Study.

This study aimed to investigate the long-term impacts of disclosing amyloid status for a risk of Alzheimer disease (AD) to cognitively normal research participants with subjective cognitive decline (SCD), which represents an initial manifestation of AD. Forty-two participants were classified as the amyloid-positive ( = 10) or amyloid-negative ( = 32) groups. We assessed symptoms of anxiety, depression, and test-related distress at 6, 24, and 52 weeks after results disclosure.

Can we predict amyloid deposition by objective cognition and regional cerebral blood flow in patients with subjective cognitive decline?

Background: Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD.

Advantages of Staged Angioplasty in a Patient with Internal Carotid Artery Pseudo-Occlusion Besides Prevention of Cerebral Hyperperfusion Syndrome.

Background: Staged angioplasty for carotid artery stenosis has been reported to be effective in preventing postoperative cerebral hyperperfusion syndrome (CHS) in patients with severe carotid stenosis; thus, it is also recommended for patients with internal carotid artery (ICA) pseudo-occlusion, the treatment strategy for which is controversial.

Case Description: This study reports the case of an Asian man in his 50s who had motor aphasia and right-side weakness caused by pseudo-occlusion of the left ICA. After medical treatment, he underwent a staged angioplasty.

The psychological impact of disclosing amyloid status to Japanese elderly: a preliminary study on asymptomatic patients with subjective cognitive decline.

ABSTRACTIn Japan, 4.6 million people are living with dementia and the number is expected to rise to 7 million by 2025. Amyloid-β (Aβ) positron emission tomography (PET) is used for cognitively normal Japanese people with or without subjective cognitive decline (SCD) for the purpose of clinical trials or diagnosis.

Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson's Disease without Dementia.

Background: Most cases of dementia with Lewy bodies (DLB) show Alzheimer's disease pathology-like senile plaques and neurofibrillary tangles. Several studies have also revealed a high prevalence of positive amyloid imaging with positron emission tomography (PET) in DLB and moderate prevalence in Parkinson's disease (PD) with dementia. However, it remains unclear in PD without dementia as to when the brain β amyloid (Aβ) burden begins and progresses.

[Transient epileptic amnesia].

Transient amnesia is one of common clinical phenomenon of epilepsy that are encountered by physicians. The amnestic attacks are often associated with persistent memory disturbances. Epilepsy is common among the elderly, with amnesia as a common symptom and convulsions relatively uncommon.

Magnetic properties of 1:2 mixed cobalt(II) salicylaldehyde Schiff-base complexes with pyridine ligands carrying high-spin carbenes (Scar = 2/2, 4/2, 6/2, and 8/2) in dilute frozen solutions: role of organic spin in heterospin single-molecule magnets.

The 1:2 mixtures of Co(p-tolsal)2, p-tolsal = N-p-tolylsalicylideniminato, and diazo-pyridine ligands, DXpy; X = 1, 2, 3l, 3b, and 4, in MTHF solutions were irradiated at cryogenic temperature to form the corresponding 1:2 cobalt-carbene complexes Co(p-tolsal)2(CXpy)2, with Stotal = 5/2, 9/2, 13/2, 13/2, and 17/2, respectively. The resulting Co(p-tolsal)2(CXpy)2, X = 1, 2, 3l, 3b, and 4, showed magnetic behaviors characteristic of heterospin single-molecule magnets with effective activation barriers, Ueff/kB, of 40, 65, 73, 72, and 74 K, for reorientation of the magnetic moment and temperature-dependent hysteresis loops with a coercive force, Hc, of ∼0, 6.2, 10, 6.

[Successful thrombolysis without hemorrhage in a patient with cardioembolic stroke under dabigatran treatment-a case report and review of literature].

A 72-year-old male with heart failure was admitted to our hospital. Treatment with dabigatran (220 mg per day) was initiated because of atrial fibrillation. On the third day, the patient developed left-sided hemiparesis and dysarthria at 4.

Enhanced aggregation of androgen receptor in induced pluripotent stem cell-derived neurons from spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor (AR) gene. Ligand-dependent nuclear accumulation of mutant AR protein is a critical characteristic of the pathogenesis of SBMA. SBMA has been modeled in AR-overexpressing animals, but precisely how the polyglutamine (polyQ) expansion leads to neurodegeneration is unclear.

Magnetic properties of 1 : 4 complexes of CoCl2 and pyridines carrying carbenes (S(0) = 4/2, 6/2, and 8/2) in diluted frozen solution; influence of carbene multiplicity on heterospin single-molecule magnets.

The microcrystalline sample of a parent complex, [CoCl(2)(py)(4)], showed a single-molecule magnet (SMM) behavior with an effective activation barrier, U(eff)/k(B), of 16 K for reversal of the magnetism in the presence of a dc field of 3 kOe. Pyridine ligands having 2-4 diazo moieties, DYpy; Y = 2, 3l, 3b, and 4, were prepared and confirmed to be quintet, septet, septet, and nonet in the ground state, respectively, after irradiation. The 1 : 4 complexes, CoCl(2)(DYpy)(4); Y = 2, 3l, 3b, and 4 in frozen solutions after irradiation showed the magnetic behaviors of SMMs with total spin multiplicity, S(total) = 17/2, 25/2, 25/2, and 33/2, respectively.

Modeling familial Alzheimer's disease with induced pluripotent stem cells.

Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance. Mutations of presenilin 1 (PS1) and presenilin 2 (PS2) are causative factors for autosomal-dominant early-onset familial AD (FAD). Induced pluripotent stem cell (iPSC) technology can be used to model human disorders and provide novel opportunities to study cellular mechanisms and establish therapeutic strategies against various diseases, including neurodegenerative diseases.

[Advances in induced pluripotent stem cell research for neurological diseases].

In 2006, Takahashi and Yamanaka reported a groundbreaking study showing mouse and human somatic cells that can be reprogrammed to the pluripotent state by expression of only a few transcription factors (Oct4, Sox2, Klf4, and c-Myc). This novel strategy can be used for transplantation therapies without immune rejection providing additional advantages regarding ethic issues of oocyte donation. For neurological diseases, disease-specific induced pluripotent stem (iPS) cells may serve as an invaluable model for clarifying pathogenesis and for screening new drug therapies.

Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease.

The identity and functional potential of dopamine neurons derived in vitro from embryonic stem cells are critical for the development of a stem cell-based replacement therapy for Parkinson's disease. Using a parthenogenetic primate embryonic stem cell line, we have generated dopamine neurons that display persistent expression of midbrain regional and cell-specific transcription factors, which establish their proper identity and allow for their survival. We show here that transplantation of parthenogenetic dopamine neurons restores motor function in hemi-parkinsonian, 6-hydroxy-dopamine-lesioned rats.

Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin.

It is currently not known whether dopamine (DA) neurons derived from human embryonic stem cells (hESCs) can survive in vivo and alleviate symptoms in models of Parkinson disease (PD). Here, we report the use of Noggin (a bone morphogenic protein antagonist) to induce neuroectodermal cell development and increase the yield of DA neurons from hESCs. A combination of stromal-derived inducing activity and Noggin markedly enhanced the generation of neuroepithelial progenitors that could give rise to DA neurons.

In vivo PET measurements with [11C]PE2I to evaluate fetal mesencephalic transplantations to unilateral 6-OHDA-lesioned rats.

Positron emission tomography (PET) is a useful tool to assess and visualize neurotransmissions in vivo. In this study, we performed repeated PET scans with [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of the expression of dopamine (DA) transmission component after a fetal mesencephalic transplantation. The fetal mesencephalic cells were transplanted into the striatum of unilateral 6-OHDA-lesioned rats.

Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats.

We evaluated correlation between neurochemical and functional alterations of the nigrostriatal dopaminergic system in rat brains lesioned with 6-hydroxydopamine (6-OHDA), that model hemi-Parkinson's disease (PD), by using three different quantitative in vivo and in vitro methods. Rats unilaterally lesioned with different doses of 6-OHDA underwent two types of in vivo experiments: (1) a rotational behavioral study with methamphetamine (MAP) or apomorphine (APO); and (2) a positron emission tomography (PET) study with [11C]PE2I (radioligand for dopamine transporters) or [11C]raclopride (radioligand for dopamine D2 receptors). An in vitro autoradiographic study with the same radioligands was also conducted.

Establishment of novel embryonic stem cell lines derived from the common marmoset (Callithrix jacchus).

The successful establishment of human embryonic stem cell (hESC) lines has inaugurated a new era in regenerative medicine by facilitating the transplantation of differentiated ESCs to specific organs. However, problems with the safety and efficacy of hESC therapy in vivo remain to be resolved. Preclinical studies using animal model systems, including nonhuman primates, are essential to evaluate the safety and efficacy of hESC therapies.

Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells.

Embryonic stem (ES) cells differentiate into dopamine (DA)-producing neurons when co-cultured with PA6 stromal cells, but the resulting cultures contain a variety of unidentified cells. In order to label live DA neurons in mixed populations, we introduced a GFP reporter under the control of the tyrosine hydroxylase (TH) gene promoter into ES cells. GFP expression was observed in TH-immunoreactive cells that differentiated from the ES cells that carried the TH-GFP reporter gene.