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.
View Article and Find Full Text PDFIntroduction: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) manifest with variable clinical features. We initiated a multicenter prospective registry study-the Japanese Longitudinal Biomarker Study in PSP and CBD-in November 2014 at 45 Japanese institutions to collect clinical information and biological samples to elucidate the natural courses and diagnostic biomarkers of PSP/CBD.
Methods: Initial symptoms, clinical features, and scores (Progressive Supranuclear Palsy Rating Scale [PSPRS], Barthel Index, Mini-Mental State Examination, and Frontal Assessment Battery) of patients clinically diagnosed with PSP/corticobasal syndrome (CBS) at the first registration were analyzed.
Background: Tau accumulation in the nucleus basalis of Meynert (nbM) has been documented in Alzheimer's disease (AD), but its relationship to neuropathological changes in other brain regions and cognitive deficits remains unclear, particularly between early-onset AD (EOAD) and late-onset AD (LOAD).
Objective: To evaluate tau accumulation patterns in the nbM and other brain regions in EOAD and LOAD using F-florzolotau PET and examine correlations with cognitive function.
Methods: Thirty-eight amyloid-positive AD patients (15 EOAD, 23 LOAD) and 46 healthy controls underwent F-florzolotau PET.
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.
View Article and Find Full Text PDFObjective: 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.
View Article and Find Full Text PDFAim: 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.
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.
View Article and Find Full Text PDFIn 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).
View Article and Find Full Text PDFObjective: 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.
View Article and Find Full Text PDFEarly diagnosis of Alzheimer's disease (AD) relies on imaging and fluid biomarkers to objectively detect and quantitatively evaluate brain AD pathologies. Amyloid- and tau-PET scans recently enabled clinicians to make definitive diagnoses based on abnormal amyloid/tau deposition in the human brain. Since PET scans and blood-based biomarkers are mutually complementary, the identification of suitable blood-based biomarkers is essential for screening brain AD pathologies.
View Article and Find Full Text PDFObjective: 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.
Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS.
Methods: An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS.
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).
Background: We recently developed a positron emission tomography (PET) probe, [ F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias-free quantitative evaluation of tau images without a priori disease information is needed.
Objective: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities.
The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013.
View Article and Find Full Text PDFThe Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013.
View Article and Find Full Text PDFThere are a variety of neurodegenerative diseases that require differentiation from idiopathic normal pressure hydrocephalus(iNPH), including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration. As the clinical features and structural imaging findings of these diseases may overlap with iNPH, biomarkers reflecting disease-specific pathology are necessary for differential diagnosis. In addition, these diseases often coexist with iNPH in elderly patients, and it is important to confirm the coexistence of their pathology even in cases clinically diagnosed as iNPH.
View Article and Find Full Text PDFBackground 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.
The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013.
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