Publications by authors named "Hiroyuki Hatsuta"
Visual hallucinations in Parkinson's disease: The critical role of intermediate nucleus basalis of Meynert.
Parkinsonism Relat Disord
August 2025
Background And Objective: Patients with Parkinson's disease (PD) often experience visual hallucinations (VH) and delusions. PD patients with VH reportedly have a higher incidence of dementia than PD patients without VH. The nucleus basalis of Meynert (nbM) comprises acetylcholine-releasing neurons that are critical for memory, attention, and arousal.
View Article and Find Full Text PDFWe previously reported a clinicopathological examination in the Sagamihara family, familial PD with LRRK I2020T mutation, highlighting the most common neuropathological finding as pure nigral degeneration without Lewy bodies (LBs). We applied immunohistochemical analysis to seven previously reported cases and evaluated five additional cases for a full neuropathological examination (altogether 12 cases). All cases exhibited nigral degeneration with a relatively preserved locus coeruleus (LC).
View Article and Find Full Text PDFAssociation of rare missense variants with Alzheimer's disease in the Japanese population.
J Alzheimers Dis
July 2025
BackgroundLittle is known about the rare missense variants (RMVs) of in East Asians, including the Japanese, and their association with Alzheimer's disease (AD) and lipid metabolism.ObjectiveTo identify RMVs in the Japanese population and investigate their association with AD and lipid metabolism, including low-density lipoprotein cholesterol levels.Methods RMVs were explored in the Niigata (NIG; 2589 subjects) and Tohoku (ToMMo; 3307 subjects) cohorts.
View Article and Find Full Text PDFAn autopsy case of type A FTLD-TDP with a GRN mutation presenting with the logopenic variant of primary progressive aphasia at onset and with corticobasal syndrome subsequently.
Takafumi Tomenaga
,
Shinobu Minatani
,
Hiroto Namba
,
Akitoshi Takeda
,
Takahito Yoshizaki
,
Hiroyuki Hatsuta
Neuropathology
February 2025
Article Synopsis
- A 68-year-old woman showed language difficulties and neurological symptoms, leading to a diagnosis of the logopenic variant of primary progressive aphasia with additional complications such as ideomotor apraxia and Gerstmann syndrome.
- After a year, she developed features consistent with corticobasal syndrome, but treatment with L-dopa was ineffective.
- Brain imaging revealed significant cortical atrophy and post-mortem analysis showed specific neuronal changes related to frontotemporal lobar degeneration with TDP-43 pathology, confirming the diagnosis of type A FTLD-TDP.
Article Synopsis
- Progressive multifocal leukoencephalopathy (PML) is a serious brain disease linked to JC virus infecting brain cells, manifesting in a 71-year-old woman after treatment for lymphoma.
- Magnetic resonance imaging showed significant iron deposits in the brain's white matter, with a confirmed PML diagnosis through a positive PCR test for the JC virus.
- The patient sadly passed away six months later, with autopsy revealing extensive brain damage and notable findings of iron-laden cells in the affected regions, marking a unique case of PML following lymphoma treatment.
Article Synopsis
- Aβ1-42 and Aβ1-43 are processed by γ-secretase into shorter Aβ peptides (Aβ1-38 and Aβ1-40), with their production and deposition in human brains correlating to Alzheimer's disease progression.
- As Alzheimer's disease advances, the levels of deposited Aβ1-43 increase in proportion to Aβ1-42, while Aβ1-38 correlates with Aβ1-40, indicating related mechanisms of deposition.
- The study reveals that γ-secretase activity varies in Alzheimer’s disease brains, leading to increased production of certain Aβs, highlighting its role in the disease pathology.
Corrigendum: Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects.
Front Aging Neurosci
November 2019
Article Synopsis
- This document serves to correct information in the original article identified by the DOI 10.3389/fnagi.2019.00222.
- The correction may address errors or inaccuracies in the data or analysis presented in the original publication.
- Readers are encouraged to refer to the corrected version for accurate information and insights.
Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects.
Front Aging Neurosci
September 2019
Article Synopsis
- Amyloid plaques and neurofibrillary tangles, related to Alzheimer's disease, were analyzed in 391 cognitively normal subjects aged 23 to 91 to understand how age affects plasma levels of specific biomarkers (Aβ40, Aβ42, and t-Tau) using an immunomagnetic reduction assay.
- There were modest correlations between the plasma levels of t-Tau and Aβ42 with age, along with significant positive correlations between Aβ42 and t-Tau in individuals aged 50 and older.
- Negative correlations were observed between Aβ40 and both t-Tau and Aβ42 in various age groups, revealing unique relationships among these biomarkers that highlight the influence of aging on Alzheimer's-related indicators.
Article Synopsis
- * Researchers found that a type of DNA change called noncoding CGG repeat expansions was behind a disease called neuronal intranuclear inclusion disease (NIID).
- * They also discovered similar DNA changes in two other diseases, showing how important it is to look for these repeat expansions to understand and find the causes of various illnesses.
Tau and TDP-43 accumulation of the basal nucleus of Meynert in individuals with cerebral lobar infarcts or hemorrhage.
Acta Neuropathol Commun
March 2019
Article Synopsis
- A study found that large strokes in the middle cerebral artery (MCA) can lead to the formation of neurofibrillary tangles (NFTs) in a specific brain area called the basal nucleus of Meynert (BNM).
- The research analyzed 31 cases (19 MCA infarcts and 12 putaminal hemorrhages) and found that a high percentage (74-100%) showed more NFTs on the affected side of the BNM than the unaffected side.
- Most NFTs appeared to develop within 5-10 years after the stroke, and a correlation was identified with another protein (TDP43) present in higher amounts on the affected side, indicating a relationship between stroke severity and neurodegenerative changes.
Article Synopsis
- Globular glial tauopathy (GGT) is a condition characterized by the accumulation of 4-repeat tau proteins, leading to globular glial inclusions, mainly in oligodendroglia.
- A 78-year-old woman exhibited symptoms of limb weakness and cognitive decline for 8 years, with imaging revealing iron deposits in her brain.
- Upon autopsy, significant brain atrophy and iron deposition were observed, confirming the diagnosis of GGT, marking the first documented case with verified iron deposits both through imaging and pathological examination.
Article Synopsis
- DLB and AD are the most common types of dementia, and patients with both conditions have a faster cognitive decline and higher mortality rates.
- Researchers studied cerebrospinal fluid (CSF) samples to find reliable biomarkers that could help distinguish between DLB, AD, and cases where they coexist.
- Findings showed that levels of certain chemicals (HVA and 5-HIAA) in CSF were significantly lower in advanced Lewy body disorders and could be used, along with other brain proteins, to accurately differentiate between the types of dementia.
Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease.
Acta Neuropathol Commun
January 2017
Article Synopsis
- MicroRNAs (miRNAs) show promise as blood-based biomarkers for Alzheimer's disease (AD) due to their stability in blood samples.
- In a study involving 45 serum samples from AD patients and controls, three specific miRNAs were found to be significantly deregulated, with hsa-miR-501-3p being validated as a potential biomarker.
- Hsa-miR-501-3p was downregulated in AD patient serum but upregulated in their brains, indicating it relates to pathological changes in AD and correlates with cognitive decline.
Excess APP O-glycosylation by GalNAc-T6 decreases Aβ production.
Keiko Akasaka-Manya
,
Masaki Kawamura
,
Hiroki Tsumoto
,
Yuko Saito
,
Yuriko Tachida
,
Hiroyuki Hatsuta
J Biochem
January 2017
Article Synopsis
- Researchers found that changes in O-glycans, a type of carbohydrate on proteins, are linked to Alzheimer's disease (AD), particularly focusing on a family of enzymes known as GalNAc-Ts involved in O-glycan synthesis.
- They discovered that the expression levels of certain GalNAc-T enzymes changed as sporadic AD progressed, with GalNAc-T6 notably reducing the production of amyloid-beta (Aβ), a protein associated with AD.
- The study indicates that GalNAc-T6's action on the amyloid precursor protein (APP) is significant and suggests that increased O-glycosylation from GalNAc-T6 may inhibit Aβ production, offering potential insights into therapeutic strategies for
Article Synopsis
- CARASIL is a hereditary brain disease linked to mutations in the HTRA1 gene, leading to unique vascular changes and brain damage.
- Three autopsied patients showed similar brain artery abnormalities regardless of their specific HTRA1 mutations, indicating a consistent neuropathological pattern.
- One patient also exhibited atherosclerosis-like changes in other body organs, suggesting the systemic effects of HTRA1 mutations extend beyond the brain's vasculature.
Article Synopsis
- The study investigates the loss of intermediolateral nucleus (IML) neurons in patients with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) to understand its role in orthostatic hypotension (OH).
- Compared to normal controls, significant reductions in IML neurons and fine myelinated fibers were observed in all three patient groups, with more severe loss in those experiencing OH.
- The findings provide neuropathological evidence that the degeneration of IML neurons and myelinated fibers is linked to autonomic dysfunction in these neurodegenerative diseases, especially in individuals with OH.
Early Stage of Progressive Supranuclear Palsy: A Neuropathological Study of 324 Consecutive Autopsy Cases.
J Nippon Med Sch
November 2016
Article Synopsis
- Diagnosing clinical progressive supranuclear palsy (PSP) is difficult, and researchers suspect that more cases exist undetected due to unclear initial lesions and progression of the disease.
- In a study of 324 autopsy patients, 35 showed signs of PSP-related tau structures, with 8 identified as pure PSP-type tauopathy after excluding certain other diagnoses.
- The incidence of pure PSP-type tauopathy was found to be 2.5%, indicating it may represent early, preclinical stages of PSP, a novel finding that needs more research to understand its causes and mechanisms.
Article Synopsis
- Tauopathies are neurodegenerative diseases marked by tau protein aggregates that are hyperphosphorylated, but the exact process and extent of tau phosphorylation in both healthy and diseased brains are unclear.
- Using Phos-tag SDS-PAGE, researchers discovered that nonphosphorylated 0N4R tau isoform is the most prevalent in adult mouse brains, while phosphorylated forms are more common in perinatal mice and stressed mice.
- In elderly human brains, nonphosphorylated forms of tau were also dominant, with slightly increased phosphorylation in Alzheimer’s patients at an advanced disease stage, suggesting that hyperphosphorylation occurs mainly in aggregated tau proteins.
Distribution of α-synuclein in the spinal cord and dorsal root ganglia in an autopsy cohort of elderly persons.
Acta Neuropathol Commun
September 2015
Article Synopsis
- The study highlights the distribution of Lewy body-related α-synucleinopathy (LBAS) in the spinal cord and its connection to the lower brainstem regions in Parkinson's disease patients.
- It was found that LBAS spreads retrogradely from the dorsal horn of the spinal cord to the dorsal root ganglia, indicating a specific pathway of progression through primary sensory neurons.
- Additionally, LBAS in sympathetic ganglia occurs before it impacts the thoracic spinal cord, suggesting that it also spreads through preganglionic sympathetic nerves.
Article Synopsis
- Protein inclusions in neurodegenerative diseases are linked to p62, which aids in clearing damaged proteins via autophagy.
- Phosphorylation of p62 at S403 enhances selective autophagy and shows accumulations in brains from amyotrophic lateral sclerosis and Alzheimer's disease cases.
- In mouse models with impaired autophagosome formation, like Atg5CKO and HD190QG, there was a reduction in S403-phos-p62 post-mortem, indicating the need to consider changes over time when analyzing human brain samples.
Article Synopsis
- TDP-43 is a key protein found in brain degeneration disorders like frontotemporal lobar degeneration and ALS, and its accumulation is also noted in other diseases like Alzheimer's and Lewy body disease, but research on its incidence in aging is limited.
- A study analyzed 286 autopsy brain samples, revealing that TDP-43 structures were present in 40% of control elderly brains and at higher rates in AD (72.4%), LBD (72.7%), and AGD (54.5%) brains, with most being dystrophic neurites (DNs) found primarily in the hippocampus.
- The results suggest that TDP-43 DNs may arise from normal aging processes,
Article Synopsis
- The case report discusses a 35-year-old male with anti-NMDAR encephalitis who experienced atypical relapses characterized by multiple white matter lesions and psychiatric symptoms.
- A brain biopsy revealed demyelinated lesions resembling those seen in multiple sclerosis, and treatment with methylprednisolone improved his condition.
- The study suggests that changes in the patient's symptoms correlated with fluctuations in the cerebrospinal fluid NMDAR antibody levels, indicating that the lesions may be a result of the encephalitis.