Quantification of monoamine oxidase B expression with C-SL25.1188 for imaging reactive astrocytes in patients with Alzheimer's disease.

Purpose: Astrocyte reactivation can be assessed using positron emission tomography (PET) ligands targeting monoamine oxidase B (MAO-B). C-SL25.1188 binds reversibly to MAO-B, allowing precise density measurements, but requires invasive arterial sampling.

Virtual reality navigation for the early detection of Alzheimer's disease.

Objective: The development of non-invasive clinical diagnostics is paramount for the early detection of Alzheimer's disease (AD). Neurofibrillary tangles in AD originate from the entorhinal cortex, a cortical memory area that mediates navigation via path integration (PI). Here, we studied correlations between PI errors and levels of a range of AD biomarkers using a 3D virtual reality navigation system to explore PI as a non-invasive surrogate marker for early detection.

Assessment of Cognitive Function via Biomarkers in Japanese Patients With Chronic Heart Failure Treated With Angiotensin-Receptor-Neprilysin Inhibitor.

Background: Angiotensin-receptor-neprilysin inhibitors (ARNIs) improve outcomes in patients with chronic heart failure (CHF). However, neprilysin is a major amyloid beta (Aβ)-degrading enzyme in the brain and although previous studies suggest that ARNI use does not induce neurocognitive dysfunction in CHF patients, data in Japanese patients are limited.

Methods And Results: This single-center, prospective, observational study enrolled 15 CHF patients: 6 who were being treated with ARNI (ARNI) and 9 who were not (non-ARNI).

Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays.

Introduction: Late-life mood disorders (LLMDs) may represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer's disease (AD) and non-AD tau pathologies in LLMD participants.

Methods: Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using F-florzolotau and C-Pittsburgh compound B.

CSF GPNMB in Parkinson's disease: A potential association with age and microglial activation.

Background: Recent evidence suggests a link between glycoprotein non-metastatic melanoma protein B (GPNMB) and Parkinson's disease (PD) pathogenesis. Although elevated plasma GPNMB levels associated with disease severity have been reported in PD, cerebrospinal fluid (CSF) alterations remain elusive.

Objective: To explore CSF GPNMB alterations and its clinical significance in PD.

-Linked Parkinson Syndrome in Female Heterozygotes Is Associated With PET-Detectable Tau Pathology.

Background And Objectives: A previous postmortem study of men with Christianson syndrome, a disorder caused by loss-of-function mutations in the gene , reported a mechanistic link between pathologic tau accumulation and progressive symptoms such as cerebellar atrophy and cognitive decline. This study aimed to characterize the relationships between neuropathologic manifestations and tau accumulation in heterozygous women with mutation.

Methods: We conducted a multimodal neuroimaging and plasma biomarker study on 3 middle-aged heterozygous women with mutations (proband 1: mid-50s; proband 2: early 50s; proband 3: mid-40s) presenting with progressive extrapyramidal symptoms.

Comparison between DSQIID total / sub-item scores and plasma p-tau elevation in adults with Down's syndrome.

The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) is an appropriate screening tool for detecting dementia in Down's syndrome patients. However, whether this questionnaire reflects the neuropsychiatric signs of biomarker-confirmed Alzheimer's disease in DS (DS-AD) remains unknown. To address this issue, we compared the plasma phosphorylated tau (P181tau: p-tau) level of a representative AD biomarker with the total score and each sub-score of the DSQIID.

Plasma biomarkers of neurodegeneration in patients and high risk subjects with Lewy body disease.

Comorbid Alzheimer's disease (AD) neuropathology is common in Lewy body disease (LBD); however, AD comorbidity in the prodromal phase of LBD remains unclear. This study investigated AD comorbidity in the prodromal and symptomatic phases of LBD by analyzing plasma biomarkers in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and individuals at risk of LBD (NaT-PROBE cohort). Patients with PD (PD group, n = 84) and DLB (DLB group, n = 16) and individuals with LBD with ≥ 2 (high-risk group, n = 82) and without (low-risk group, n = 37) prodromal symptoms were enrolled.

In Vivo Assessment of Astrocyte Reactivity in Patients with Progressive Supranuclear Palsy.

Objective: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity.

Plasma biomarkers for predicting the development of dementia in a community-dwelling older Japanese population.

Aim: To assess the association between plasma amyloid β (Aβ) 42/40, phosphorylated tau (p-τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population.

Methods: A total of 1346 Japanese community-dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years.

Validation of a newly developed immunoassay for TDP-43 in human plasma.

The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies.

Investigating neural dysfunction with abnormal protein deposition in Alzheimer's disease through magnetic resonance spectroscopic imaging, plasma biomarkers, and positron emission tomography.

In Alzheimer's disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the human brain. To clarify the relationship between neuronal dysfunction and abnormal proteins in AD-affected brains, we conducted magnetic resonance spectroscopic imaging (MRSI) and assessed the neurofilament light chain plasma levels (NfL).

Altered Brain Energy Metabolism Related to Astrocytes in Alzheimer's Disease.

Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered brain energy metabolism.

Enzymatic properties and clinical associations of serum alpha-galactosidase A in Parkinson's disease.

Objective: Recent studies have revealed an association between Parkinson's disease (PD) and Fabry disease, a lysosomal storage disorder; however, the underlying mechanisms remain to be elucidated. This study aimed to investigate the enzymatic properties of serum alpha-galactosidase A (GLA) and compared them with the clinical parameters of PD.

Methods: The study participants consisted of 66 sporadic PD patients and 52 controls.

Soluble TREM2 and Alzheimer-related biomarker trajectories in the blood of patients with diabetes based on their cognitive status.

Aim: We aimed to elucidate the dynamics of blood biomarkers according to the severity of cognitive impairment in patients with type 2 diabetes mellitus (DM) and to identify useful biomarkers for diabetes-related dementia.

Methods: This was a cross-sectional, nested case-control study of 121 Japanese DM and non-DM patients with different levels of cognitive functioning. We evaluated participants' cognitive functions, blood biomarkers related to Alzheimer's disease, and soluble triggering receptors expressed on myeloid cells 2 (sTREM2).

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis.

Background And Purpose: The aim was to investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis (ALS), and to compare cerebrospinal fluid (CSF) and serum ADMA levels with other biomarkers of ALS.

Methods: Serum ADMA levels of sporadic ALS patients (n = 68), disease control patients (n = 54) and healthy controls (n = 20) were measured using liquid chromatography tandem mass spectrometry. Correlations of the ADMA level and other markers (nitric oxide and neurofilament light chain levels) were analyzed.

Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics.

Objectives: We previously reported the diagnostic and prognostic performance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma as amyotrophic lateral sclerosis (ALS) biomarkers. The present study aimed to elucidate associations between clinical characteristics and the markers as well as mutual associations of the markers in ALS patients using the same dataset.

Methods: NfL, TDP-43, and t-tau levels in CSF and plasma in 75 ALS patients were analyzed.

Proteomic Profiling of Extracellular Vesicles Separated from Plasma of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy.

Chronic Traumatic Encephalopathy (CTE) is a tauopathy that affects individuals with a history of exposure to repetitive head impacts, including National Football League (NFL) players. Extracellular vesicles (EVs) are known to carry tau in Alzheimer's disease and other tauopathies. We examined protein profiles of EVs separated from the plasma of former NFL players at risk for CTE.

Quantification of Blood Caffeine Levels in Patients With Parkinson's Disease and Multiple System Atrophy by Caffeine ELISA.

Caffeine is considered to be a neuroprotective agent against Parkinson's disease (PD) and is expected to offer a blood-based biomarker for the disease. We herein investigated the ability of this biomarker to discriminate between PD and neurodegenerative diseases. To quantify caffeine concentrations in serum and plasma, we developed a specific competitive enzyme-linked immunosorbent assay (ELISA).