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.

A case of chronic progressive autoimmune GFAP astrocytopathy with extensive meningoencephalomyelitis and contrast enhancement on MRI.

•We herein present a case of chronic progressive autoimmune GFAP astrocytopathy.•Symmetrical high-intensity signals on FLAIR were observed in the white matter of the temporal and occipital lobes, lateral cerebral ventricle walls, hippocampus, amygdala, and occipital cortex, with extensive Gd enhancement in radial perivascular lesions and the ependyma in the choroid plexus.•Improvements were achieved by 4 courses of IVMP and one of IVIg.

Role of complement activation and disruption of the blood-brain barrier in the pathogenesis of multiple system atrophy.

Multiple system atrophy (MSA) is a progressive and sporadic neurodegenerative disorder characterized by the histological appearance of glial cytoplasmic inclusions primarily composed of α-synuclein. Recently, complement-mediated neuroinflammation has been proposed as a key factor in the pathogenesis of numerous neurodegenerative disorders. We conducted immunohistochemical/immunofluorescent assays targeting a number of complements to explore the role of complements in MSA pathogenesis using brain samples from deceased patients and controls.

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.

A comparison of cerebral amyloid angiopathy in the cerebellum and CAA-positive occipital lobe of 60 brains from routine autopsies.

We semiquantitatively compared the frequency and severity of cerebral amyloid angiopathy (CAA) in the cerebellum and CAA-positive occipital lobe of 60 subjects from routine autopsies. In the 60 subjects with a CAA-positive occipital lobe, cerebellar CAA was observed in 29 subjects (48.3%), and the severity of cerebellar CAA was relatively mild compared with occipital lobe CAA.

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.

An autopsy case of amyloid angiopathy-related cerebellar hemorrhage.

An 80-year-old man with dementia demonstrated cerebellar hemorrhage. Autopsy revealed pathology compatible with Alzheimer's disease and cerebral amyloid angiopathy (CAA). CAA was more prevalent in the occipital lobe than in the frontal, parietal, and temporal lobes; however, amyloid-β (Aβ)-containing senile plaques were less abundant in the occipital cortex than in the other cortices.

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.

Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of F-THK5351 Positron Emission Tomography: A Case Report.

In Alzheimer's disease, the apolipoprotein E gene ε2 allele is a protective genetic factor, whereas the ε4 allele is a genetic risk factor. However, both the ε2 and the ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the ε2 allele remains unknown.

Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria.

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.

Amyloid-β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly.

We examined 29 cases in which cerebral amyloid angiopathy (CAA) was detected among routine aged autopsies. Most cases with severe CAA had many amyloid-β (Aβ) plaques in the occipital cortex. Nonetheless, two cases had few Aβ plaques with many small vessels and capillaries with CAA.

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.

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology.

Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established.

Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.

Astrocytic tau pathologies in aged human brain.

Argyrophilic and tau-positive abnormal structures in astrocytes are frequent in aged brains, with a new nomenclature of aging-related tau astrogliopathy (ARTAG) proposed. The two major cytomorphologies of ARTAG are thorn-shaped astrocytes (TSA) and granular or fuzzy tau immunoreactivity in processes of astrocytes (GFA). We selected 28 cases in which many AT8-identified astrocytic tauopathies were observed in the central nervous system from 330 routine aged autopsied cases, including Alzheimer's disease.

Gullibility may be a warning sign of Alzheimer's disease dementia.

Unlabelled: ABSTRACTBackground:Theory of Mind reasoning, which plays a pivotal role in social interaction, is required to detect deception. Empirically, those with cognitive decline are vulnerable to deception.

Methods: Participants were 45 healthy elderly adults with clinical dementia rating (CDR) 0, and 76 outpatients: 25 with amnestic mild cognitive impairment (aMCI, CDR 0.

Adult moyamoya disease associated with abundant phosphorylated tau accumulation in the brainstem: Report of a case with autopsy findings.

We report the case of a 72-year-old Japanese woman with moyamoya disease (MMD). She experienced her first intracerebral hemorrhage (ICH) at the age of 32 years, and had nine ICHs and/or intraventricular hemorrhages during the following 40 years. Cerebral angiograms and vascular pathologies at autopsy confirmed that the patient suffered from MMD.

Comparison of AT8 immunoreactivity in the locus ceruleus and hippocampus of 154 brains from routine autopsies.

We compared semiquantitatively AT8 immunoreactivity in the locus ceruleus (LC) and hippocampus of 154 brains from routine autopsies to investigate the initial sites of phosphorylated tau (phospho-tau) development. The numbers of AT8-positive neurons and the severity of AT8-positive neuropil threads (NTs) in the LC were strongly associated: there were no cases with AT8-positive neurons that lacked NTs and 20 cases (13%) had only NTs in the LC. Phospho-tau pathologies in the LC were almost equally on both sides, although some cases (7.