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Adolescent binge alcohol exposure accelerates Alzheimer's disease-associated basal forebrain neuropathology through proinflammatory HMGB1 signaling.

Human studies suggest that heavy alcohol use may be an etiological factor contributing to the development of Alzheimer's disease (AD) neuropathology. Both alcohol use disorder (AUD) and AD share common underlying neuropathology, including proinflammatory high-mobility group box 1 (HMGB1)-mediated neuroimmune signaling and basal forebrain cholinergic neuron degeneration. Adolescent onset of binge drinking represents a significant risk factor for later development of an AUD, and accumulating evidence suggests that adolescent initiation of heavy alcohol use induces HMGB1 signaling and causes dege…

Advancements in diagnosing Post-concussion Syndrome: insights into epidemiology, pathophysiology, neuropathology, neuroimaging, and salivary biomarkers.

Post-Concussion Syndrome (PCS) represents a complex constellation of symptoms that persist following a concussion or mild traumatic brain injury (mTBI), with significant implications for patient care and outcomes. Despite its prevalence, diagnosing PCS presents considerable challenges due to the subjective nature of symptoms, the absence of specific diagnostic tests, and the overlap with other neurological and psychiatric conditions. This review explores the multifaceted diagnostic challenges associated with PCS, including the heterogeneity of symptom presentation, the limitations of current n

Substantia Nigra Iron Deposition in Lewy Body Disease: A Magnetic Resonance Imaging and Neuropathology Study.

OBJECTIVE: To compare iron deposition in the substantia nigra (SN) as measured with quantitative susceptibility mapping (QSM) on antemortem magnetic resonance imaging (MRI) between individuals with and without Lewy-related pathology at autopsy. METHODS: We performed a retrospective cohort study including 54 participants who underwent autopsy and antemortem MRI with QSM. Cases were classified as Lewy body disease (LBD)-present (n = 13) if they had Lewy-related pathology and LBD-absent (n = 41) if they did not have Lewy-related pathology. QSM was calculated for the whole SN and the two subregio

Brain tissue metal concentrations and Alzheimer's disease neuropathology in total joint arthroplasty patients versus controls.

We examined whether total joint arthroplasty (TJA) is associated with increased metal accumulation in the brain and histopathologic changes of Alzheimer's disease. We measured ultra-trace metal concentrations (aluminum, chromium, cobalt, manganese, molybdenum, nickel, titanium, and vanadium) on postmortem frozen tissues of the occipital lobe of 177 subjects (89 non-TJA and 88 TJA) using a triple-quadrupole inductively coupled plasma mass spectrometry and correlated elemental concentrations to the degree of Alzheimer's disease neuropathic change (ADNC). To effectively assess the relationship be

TDP-43 overexpression in the hypothalamus drives neuropathology, dysregulates metabolism and impairs behavior in mice.

TAR DNA-binding protein 43 (TDP-43) pathology is linked to the neurodegenerative disorders amyotrophic lateral sclerosis (ALS), frontotempor … her there is a casual link between the effects of TDP-43 in the hypothalamus and the development of neuropathology, as well as changes in metabolism and behavior. We generated an adeno-associated viral (AAV) vector expressing human TDP-43 under the neuronal-specific synapsin promoter, which was injected bilaterally into the hypothalamus of wild-type FVB/N mice. …

Шёпот в мозгу: внеклековые везикла в нейропотологии и диагностическая алхимия неврологических заболеваний.

Внешние клеточные везикулы (ЭМ) стали ключевыми посредниками в неврологических заболеваниях, демонстрируя многогранную потенциальную роль от патогенеза до диагноза. Эти нано-мембранные структуры, высвобождаемые различными типами клеток, включая нейроны, астроциты и микроглию, инкапсулируют разнообразный груз белков, липидов, видов РНК и даже фрагментов ДНК. В нейропатологии ЭМ вносят значительный вклад в межклеточную связь в рамках центральной нервной системы (КНС), оказывая влияние на физиологические или патологические каскады. С помощью передачи биоактивных молекул ЭВ модифицируют нейроинфла

Совпадение в аннотации оригинала
Extracellular vesicles (EVs) have emerged as pivotal mediators in neurological diseases, showcasing multifaceted potential roles ranging fro … microglia, encapsulate a diverse cargo of proteins, lipids, RNA species, and even DNA fragments. In neuropathology, EVs contribute significantly to intercellular communication within the central nervous system (CNS), influencing physiological or pathological cascades. Through the transfer of bioactive molecules, EVs modulate neuroinflammation, neuronal survival, …

Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detectio

Granulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.

Progranulin (PGRN) deficiency is linked to neurodegenerative diseases, including frontotemporal dementia (FTD), Alzheimer's disease, and Parkinson's disease. Proper PGRN levels are critical for brain health; however, the function of PGRN is unclear. PGRN is composed of 7.5 repeat domains, called granulins, and processed into granulins inside the lysosome. PGRN is beneficial for neuronal health, but the role of individual granulins is controversial and unclear. We find that the expression of single granulins broadly rescues disease pathology in Grn-/- mice. Adeno-associated virus (AAV)-mediated

Proteomimetic polymer blocks mitochondrial damage, rescues Huntington's neurons, and slows onset of neuropathology in vivo.

Recently, it has been shown that blocking the binding of valosin-containing protein (VCP) to mutant huntingtin (mtHtt) can prevent neuronal mitochondrial autophagy in Huntington's disease (HD) models. Herein, we describe the development and efficacy of a protein-like polymer (PLP) for inhibiting this interaction in cellular and in vivo models of HD. PLPs exhibit bioactivity in HD mouse striatal cells by successfully inhibiting mitochondrial destruction. PLP is notably resilient to in vitro enzyme, serum, and liver microsome stability assays, which render analogous control oligopeptides ineffec

Learning pyramidal multi-scale harmonic wavelets for identifying the neuropathology propagation patterns of Alzheimer's disease.

Previous studies have established that neurodegenerative disease such as Alzheimer's disease (AD) is a disconnection syndrome, where the neuropathological burdens often propagate across the brain network to interfere with the structural and functional connections. In this context, identifying the propagation patterns of neuropathological burdens sheds new light on understanding the pathophysiological mechanism of AD progression. However, little attention has been paid to propagation pattern identification by fully considering the intrinsic properties of brain-network organization, which plays

BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms

Unveiling The Neuropathology Tumour Landscape: 10-Year Statistical Analysis With Global Comparison - Single Centre Experience.

Introduction: Central nervous system (CNS) tumours represent a significant public health issue worldwide, and their incidence and distribution vary across different populations. Although studies on CNS tumours have been conducted in various countries, there is a lack of information regarding their patterns in Macedonia. Therefore, this study is aimed at investigating the distribution, histopathological types and subtypes and demographic features of CNS tumours in our country. Materials and Methods: A cross sectional study was conducted using the electronic database of the Institute of Patholog

Elevated Galectin-9 across the human brain correlates with HIV neuropathology and detrimental cognitive states.

HIV persistence and neuroinflammation are known to contribute to HIV-associated neuropathology. However, the multifaceted pathways driving impairment remain poorly understood. Galectin-glycan interactions have emerged as significant contributors to neuroinflammatory processes and may play a role in neuroHIV. Here, we quantified Galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, in post-mortem brain tissue across multiple regions from HIV-infected and HIV-uninfected donors to determine causal associations with HIV brain injury. We demonstrate that the staining intensity, total staining…

Diffuse excessive high signal intensity in the preterm brain on advanced MRI represents widespread neuropathology.

Preterm brains commonly exhibit elevated signal intensity in the white matter on T2-weighted MRI at term-equivalent age. This signal, known as diffuse excessive high signal intensity (DEHSI) or diffuse white matter abnormality (DWMA) when quantitatively assessed, is associated with abnormal microstructure on diffusion tensor imaging. However, postmortem data are largely lacking and difficult to obtain, and the pathological significance of DEHSI remains in question. In a cohort of 202 infants born preterm at ≤32 weeks gestational age, we leveraged two newer diffusion MRI models - Constrained Sp

Neuropathology of depression in non-demented older adults: A large postmortem study of 741 individuals.

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. Seven hundred forty-one individuals (age at death = 72.2 ± 11.7 years) from the Biobank for Aging Studies were analyzed. a-MDD was present in 54 (7.3%) participants, LLD in 80 (10.8%), and DS in 168 (22.7%). After adjustment for covariates and compared to controls, a-MDD, LDD and DS were associated with small vessel disease (p = 0.039, p = 0.0

Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer's-type neuropathology.

Cancer and Alzheimer's disease are common diseases in ageing populations. Previous research has reported a lower incidence of Alzheimer's disease-type (amnestic) dementia among individuals with a diagnosis of cancer. Both cancer and amnestic dementia are prevalent and potentially lethal clinical syndromes. The current study was conducted to investigate the association of cancer diagnosis with neuropathological and cognitive features of dementia. Data were analysed from longitudinally evaluated participants in a community-based cohort study of brain ageing who came to autopsy at the University

Cerebral Organoids for Modeling of HSV-1-Induced-Amyloid β Associated Neuropathology and Phenotypic Rescue.

Herpes simplex virus type I (HSV-1) infection is a potential risk factor involved in the Amyloid β (Aβ) associated neuropathology. However, further understanding of the neuropathological effects of the HSV-1 infection is hampered by the limitations of existing infection models due to the distinct differences between human brains and other mammalians' brains. Here we generated cerebral organoid models derived from pluripotent stem cells to investigate the HSV-induced Aβ associated neuropathology and the role of antiviral drugs in the phenotypic rescue. Our results identified that the HSV-1-infe…

Advances in the genetics and neuropathology of tuberous sclerosis complex: edging closer to targeted therapy.

Tuberous sclerosis complex is a rare genetic disease associated with mutations in the TSC1 or TSC2 genes, which cause overactivation of the … In the past 5 years, substantial advances have also been made in our understanding of mTOR-related neuropathology and the molecular aspects of both epileptogenesis and co-occurring neurodevelopmental disorders. Many potential disease-modifying strategies have been identified, including developments in targeted therapies based on molecular findings in epilepsy. …

Neuropathology Evaluation of in Utero Correction of Myelomeningocele and Complications of Late-Onset GBS Infection.

Background: Myelomeningocele (MMC) causes significant morbidity and mortality. Efforts have been directed to correct this defect in utero. The neuropathology literature on antenatally repaired MMC and associated complications in humans is limited. Case report: A 12-day-old female, who underwent prenatal MMC repair via a two-layer closure (dural replacement patch, primary skin closure), was born at 34 weeks' gestation. Her group B streptococcus positive mother received appropriate antepartum prophylactic antibiotics. She remained stable until day 11 of life when she underwent rapid clinical det…