János Bencze

Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

A Lewy-testes demencia klinikai és neuropatológiai jellemzői

Absztrakt: A Lewy-testes demencia a masodik leggyakoribb neurodegenerativ demencia. A pontos diagnozisa gyakran csak neuropatologiai vizsgalattal lehetseges. A betegseg fő morfologiai jellemzője a koros α-szinukleinben gazdag Lewy-test es Lewy-neurit – csakugy, mint a rokon korkep Parkinson-kor es az ahhoz tarsulo demencia eseten. A patomechanizmus fontos tenyezői a neurotranszmitter rendszerek zavara, a szinaptikus diszfunkcio es az ubikvitin-proteaszoma rendszer elegtelen műkodese. Jellemző a kognitiv teljesitmeny fluktuacioja, parkinsonizmus es vizualis hallucinacio. Mivel gyakran nem tipusos a klinikai kep es időbeni lefolyas, a kepalkoto eljarasok es biomarkerek elősegithetik a korai felismerest. Noha hatekony oki terapia nincs, eletminőseget javito kezelesek lehetsegesek. A klinikopatologiai vizsgalatok kiemelten fontosak a patomechanizmus jobb megertese, a pontos diagnozis es a hatekony terapia erdekeben. Orv Hetil. 2017; 158(17): 643–652.Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. The accurate diagnosis is often possible only by neuropathological examination. The morphologic hallmarks are the presence of α-synuclein-rich Lewy bodies and Lewy neurites, identical to those seen in Parkinsons disease (PD) and Parkinsons disease dementia (PDD). Neurotransmitter deficits, synaptic and ubiquitin-proteasome system (UPS) dysfunction play major role in the pathomechanism. Characteristic symptoms are cognitive fluctuation, parkinsonism and visual hallucinations. Due to the often atypical clinical presentation novel imaging techniques and biomarkers could help the early diagnosis. Although curative treatment is not available, therapies can improve quality of life. Clinicopathological studies are important in exploring pathomechanisms, ensuring accurate diagnosis and identifying therapeutic targets. Orv Hetil. 2017; 158(17): 643-652.

The melanin-concentrating hormone system in human, rodent and avian brain

Abstract Melanin-concentrating hormone (MCH) is a cyclic 19 amino acid orexigenic hypothalamic peptide. MCH is located in the lateral and dorsal hypothalamus, as well as in the zona incerta. In mammals MCH increases food intake, contributes to regulation of energy balance, temperature, reproductive function, endocrine homeostasis and biological rhythms. Several studies have proved the significance of MCH in obesity, diabetes and depression. Although the peptide is well-characterized in mouse models, much less is known about its functions in avians. In birds the MCH system especially in the lateral and basal hypothalamus has important connections to the limbic system and it coordinates the vegetative and endocrine functions, as well as the emotional behaviour. Pharmacological modulation of MCH system could contribute to the therapy of eating disorders and improve agricultural efficiency regarding avians. Reviewing the current knowledge on MCH system in human, rodents and avians may stimulate a new wave of studies in the field.

Biological function of Lemur tyrosine kinase 2 (LMTK2): Implications in neurodegeneration

Neurodegenerative disorders are frequent, incurable diseases characterised by abnormal protein accumulation and progressive neuronal loss. Despite their growing prevalence, the underlying pathomechanism remains unclear. Lemur tyrosine kinase 2 (LMTK2) is a member of a transmembrane serine/threonine-protein kinase family. Although it was described more than a decade ago, our knowledge on LMTK2’s biological functions is still insufficient. Recent evidence has suggested that LMTK2 is implicated in neurodegeneration. After reviewing the literature, we identified three LMTK2-mediated mechanisms which may contribute to neurodegenerative processes: disrupted axonal transport, tau hyperphosphorylation and enhanced apoptosis. Moreover, LMTK2 gene expression is decreased in an Alzheimer’s disease mouse model. According to these features, LMTK2 might be a promising therapeutic target in near future. However, further investigations are required to clarify the exact biological functions of this unique protein.

Advanced cerebral amyloid angiopathy and small vessel disease are associated with psychosis in Alzheimer’s disease

Psychotic symptoms may occur in any dementia, including Alzheimer’s disease (AD), but are particularly common in Lewy body dementia (LBD). The mechanisms of psychotic symptoms are largely unknown. Psychosis has been found to be associated with more severe AD and Lewy body pathology in patients with AD and cerebrovascular disease-related vasculopathy.1 One form of vascular pathology, cerebral amylod angiopathy (CAA), is defined as deposits of amyloid in the vessel walls that increase risk of haemorrhage and ischaemia. CAA contributes to neurodegeneration, but its relation to clinical symptoms and course in dementia is not fully understood.2 The aim of this study was to investigate the postmortem pathological correlates of severe psychotic symptoms in moderate AD and LBD, which were followed annually from the time of diagnosis until death. This is a 12-year prospective follow-up study of dementia ending in neuropathological examination. The 223 patients of the dementia study in Western Norway (Demvest) were diagnosed as mild dementia and followed annually with standardised clinical assessments until death. Patient were diagnosed according to standardised clinical criteria for AD3 and DLB4 or Parkinsons disease dementia (PDD) (both combined as LBD) and mild dementia defined as Mini Mental Status Examination (MMSE) score of at least 20 or a Clinical Dementia Rating scale(CDR) global score=1. The procedures are described in detail elsewhere.5 All comparisons are between groups are based on pathological defined diagnosis. The validated Norwegian 12-item Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. Presence of severe psychosis was based on the first 5 years after diagnosis and MMSE value above 10. NPI score of >4 on either item 1 (delusions) or 2 (hallucinations) was used as clinical significant cut-off. …

Pathophysiology of meningioma growth in pregnancy

Abstract Meningioma is among the most frequent brain tumours predominantly affecting elderly women. Epidemiological studies have shown that at the age of fertility the incidence is relatively low. The biological behaviour of meningioma in pregnancy is different from other meningiomas. The possible explanation is rooted in the complex physiological changes and hormonal differences during pregnancy. The increased meningioma growth observed in pregnancy is presumably the result of endocrine mechanisms. These include increase in progesterone, human placental lactogen (hPL) and prolactin (PRL) serum levels. In contrast, levels of pituitary hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotropin (hCG) produced by the placenta are decreasing in the mother prior to childbirth. Besides, vascular factors also play a crucial role. Peritumoral brain edema (PTBE), with well-known causative association with vascular endothelial growth factor (VEGF), can often be seen both with imaging and in the surgical specimens. Our aim is to assess published research on this topic including diagnostic and therapeutic guidelines, and to provide a clinically useful overview on the pathophysiology and biological behaviour of this rare complication of pregnancy.

Az extracelluláris mátrix rendellenességei epithelialis-stromalis és stromalis cornealis dystrophiákban

The human cornea is rich in extracellular matrix. The stroma constitutes the main thickness of the cornea, which consists of collagens and proteoglycans mainly. The epithelial-stromal and stromal dystrophies of the cornea are either autosomal dominant or recessive inherited disorders, which are unrelated to inflammation or trauma. The diseases can manifest in each layer of the cornea, but in most cases the corneal stroma is affected. Generally, they develop in childhood or young adulthood but the diagnosis is only possible when clinical signs (epithelial erosions, decreased visual acuity, photophobia) develop. The different protein aggregates (hyaline, amyloid, crystalline) deposited in the corneal layers result in mild or advanced corneal opacity and loss of the corneal transparency due to disorganisation of the extracellular matrix. In some of the corneal dystrophies the keratane sulphate proteoglycan looses its function which results in a loss of the regular interfibrillar spacing. Due to the severe corneal opacity patients may need corneal transplantation. Orv. Hetil., 2016, 157(33), 1299-1303.The human cornea is rich in extracellular matrix. The stroma constitutes the main thickness of the cornea, which consists of collagens and proteoglycans mainly. The epithelial-stromal and stromal dystrophies of the cornea are either autosomal dominant or recessive inherited disorders, which are unrelated to inflammation or trauma. The diseases can manifest in each layer of the cornea, but in most cases the corneal stroma is affected. Generally, they develop in childhood or young adulthood but the diagnosis is only possible when clinical signs (epithelial erosions, decreased visual acuity, photophobia) develop. The different protein aggregates (hyaline, amyloid, crystalline) deposited in the corneal layers result in mild or advanced corneal opacity and loss of the corneal transparency due to disorganisation of the extracellular matrix. In some of the corneal dystrophies the keratane sulphate proteoglycan looses its function which results in a loss of the regular interfibrillar spacing. Due to the severe corneal opacity patients may need corneal transplantation. Orv. Hetil., 2016, 157(33), 1299-1303.

A cornealis sebgyógyulás és az extracelluláris mátrix

The cornea is the first refractive element of the eye. The transparency of the cornea results from the regularly arranged collagen fibrils, forming lamellar structure and the leucin rich proteoglycans, which make interactions between the fibrils. The adult cornea consists mainly of fibril-forming collagens. The cornea has less amount of fibril associated and non-fibrillar collagens. The main proteoglycans of the cornea are keratan-sulfate proteoglycans and it also contains dermatan-sulfate proteoglycans. Disorders of the proteoglycan synthesis lead to the disruption of the unique pattern and result in thicker collagen fibrils. The abnormal structure of the extracellular matrix can generate corneal disorders and the loss of corneal transparency. Furthermore, proteoglycans and collagens have an important role in wound healing. In injury the keratocytes produce higher amounts of collagens and proteoglycans mediated by growth factors. Depending on the ratio of the cells and growth factors the extracellular matrix returns to normal or corneal scar tissue develops.The cornea is the first refractive element of the eye. The transparency of the cornea results from the regularly arranged collagen fibrils, forming lamellar structure and the leucin rich proteoglycans, which make interactions between the fibrils. The adult cornea consists mainly of fibril-forming collagens. The cornea has less amount of fibril associated and non-fibrillar collagens. The main proteoglycans of the cornea are keratan-sulfate proteoglycans and it also contains dermatan-sulfate proteoglycans. Disorders of the proteoglycan synthesis lead to the disruption of the unique pattern and result in thicker collagen fibrils. The abnormal structure of the extracellular matrix can generate corneal disorders and the loss of corneal transparency. Furthermore, proteoglycans and collagens have an important role in wound healing. In injury the keratocytes produce higher amounts of collagens and proteoglycans mediated by growth factors. Depending on the ratio of the cells and growth factors the extracellular matrix returns to normal or corneal scar tissue develops.