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Associations of cortical SPP1 and ITGAX with cognition and common neuropathologies in older adults.

INTRODUCTION: The secreted phosphoprotein 1 (SPP1) gene expressed by CD11c+ cells is known to be associated with microglia activation and neuroinflammatory diseases. As most studies rely on mouse models, we investigated these genes and proteins in the cortical brain tissue of older adults and their role in Alzheimer's disease (AD) and related disorders. METHODS: We leveraged protein measurements, single-nuclei, and RNASeq data from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) of over 1200 samples for association analysis. RESULTS: Expression of SPP1 and its encoded p

Neuropathologic Changes of Alzheimer's Disease and Related Dementias: Relevance to Future Prevention.

BACKGROUND: Decedents with late-life dementia are often found at autopsy to have vascular pathology, cortical Lewy bodies, hippocampal sclerosis, and/or TDP-43 encephalopathy alone or with concurrent Alzheimer's disease (AD) lesions. Nonetheless, it is commonly believed that AD neuropathologic changes (NC) are the dominant or exclusive drivers of late-life dementia. OBJECTIVE: Assess associations of end-of-life cognitive impairment with any one or any combination of five distinct NC. Assess impairment prevalence among subjects having natural resistance to each type of NC. METHODS: Brains fro

Dementia is associated with medial temporal atrophy even after accounting for neuropathologies.

Brain atrophy is associated with degenerative neuropathologies and the clinical status of dementia. Whether dementia is associated with atro … est to MRI. We examined the following dichotomized neuropathological variables: Alzheimer's disease neuropathology, hippocampal sclerosis, Lewy bodies, cerebral amyloid angiopathy and atherosclerosis. Voxel-based morphometry identified areas associated with dementia after accounting for neuropathologies. Identified regions of interest were further analysed. We u …

Neuropathologic and molecular aspects of a canine distemper epizootic in red foxes in Germany.

In the last fifteen years, an epidemic of canine distemper virus (CDV) with marked neurotropism has occurred in Europe after a longer period of endemic transmission. Many wildlife species have been infected, with red foxes (Vulpes vulpes) being particularly affected. Given that this species is assumed to mediate cross-species CDV infections to domestic and wild animals, tissue samples from foxes with confirmed CDV infection in North-Western Germany were investigated to better understand the neurotropic aspects of the disease. This analysis included histopathology, virus distribution and cell t

Neuropathological findings in fatal COVID-19 and their associated neurological clinical manifestations.

Severe cases of Coronavirus Disease 2019 (COVID-19) can present with multiple neurological symptoms. The available neuropathological studies have described different lesions; the most frequent was the presence of neuroinflammation and vascular-related lesions. The objective of this study was to report the neuropathological studies performed in a medical institution, with abundant long intensive care unit stays, and their associated clinical manifestations. This is a retrospective monocentric case series study based on the neuropathological reports of 13 autopsies with a wide range of illness d

Deep learning from multiple experts improves identification of amyloid neuropathologies.

Pathologists can label pathologies differently, making it challenging to yield consistent assessments in the absence of one ground truth. To address this problem, we present a deep learning (DL) approach that draws on a cohort of experts, weighs each contribution, and is robust to noisy labels. We collected 100,495 annotations on 20,099 candidate amyloid beta neuropathologies (cerebral amyloid angiopathy (CAA), and cored and diffuse plaques) from three institutions, independently annotated by five experts. DL methods trained on a consensus-of-two strategy yielded 12.6-26% improvements by area

Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice.

BACKGROUND: Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. METHODS: We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two i

Associations of Alzheimer's Disease Neuropathologic Changes with Clinical Presentations of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) and Alzheimer's disease (AD) are the two most prevalent neurodegenerative diseases associated with age. … AD pathology on dementia, hallucinations, and dyskinesia commonly seen in advanced PD. RESULTS: AD neuropathology significantly increased the risk of hallucinations and dementia, but not dyskinesia in PD patients. Surprisingly, diffuse Lewy body pathology, but not AD pathology, was associated with the occurrence of dementia and hallucinations. Most importantly, …

Comorbid neuropathological diagnoses in early versus late-onset Alzheimer's disease.

Co-pathologies play an important role in the expression of the Alzheimer's disease clinical phenotype and may influence treatment efficacy. Early-onset Alzheimer's disease, defined as manifesting before age 65, is viewed as a relatively pure form of Alzheimer's disease with a more homogeneous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with early-onset Alzheimer's disease (median age of onset = 55 years, 44 females) and 48 with late-onset Alzheimer's disease (median age of onset = 73 years,

Association between WWOX/MAF variants and dementia-related neuropathologic endophenotypes.

The genetic locus containing the WWOX and MAF genes was implicated as a clinical Alzheimer's disease (AD) risk locus in two recent large meta-analytic genome wide association studies (GWAS). In a prior GWAS, we identified a variant in WWOX as a suggestive risk allele for hippocampal sclerosis. We hypothesized that the WWOX/MAF locus may be preferentially associated with non-plaque- and non-tau-related neuropathological changes (NC). Data from research participants with GWAS and autopsy measures from the National Alzheimer's Coordinating Center and the Religious Orders Study and the Rush Memory

Persistent bowel dysfunction after surgery for Hirschsprung's disease: A neuropathological perspective.

Hirschsprung's disease (HD) is a congenital disorder, characterized by aganglionosis in the distal part of the gastrointestinal tract. Despite complete surgical resection of the aganglionic segment, both constipation and fecal incontinence persist in a considerable number of patients with limited treatment options. There is growing evidence for structural abnormalities in the ganglionic bowel proximal to the aganglionosis in both humans and animals with HD, which may play a role in persistent bowel dysfunction. These abnormalities include: (1) Histopathological abnormalities of enteric neural

Neuropathological spectrum in systemic lupus erythematosus: A single institute autopsy experience.

AIM: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by circulating autoantibodies and immune complexes involving virtually every organ of the body. However, with respect to central nervous system (CNS), the mechanism of injury is still debated as complement mediated or thrombo-ischemic in nature. We studied the spectrum of neuropathological changes in twelve autopsy cases of SLE and evaluated the role of immune-complexes and complement activation in contributing to the thrombo-ischemic injury and correlated these features with clinical profile. METHODS: Aut

Neuropathological profile of long-duration amyotrophic lateral sclerosis in military Veterans.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Although ALS typically leads to death within 3 to 5 years after initial symptom onset, approximately 10% of patients with ALS live more than 10 years after symptom onset. We set out to determine similarities and differences in clinical presentation and neuropathology in persons with ALS with long vs. those with standard duration. Participants were United States military Veterans with a pathologically confirmed diagnosis of ALS (n = 179), dichotomized into standard d…

Characterizing Clinical and Neuropathological Traits of APOE Haplotypes in African Americans and Europeans.

BACKGROUND: The APOEɛ4 allele is the largest genetic risk factor for late-onset Alzheimer's disease (AD). Recent literature suggested that the contribution of APOEɛ4 to AD risk could be population-specific, with ɛ4 conferring a lower risk to Blacks or African Americans. OBJECTIVE: To investigate the effect of APOE haplotypes on AD risk in individuals with European ancestry (EU) and Blacks or African Americans (AA). METHODS: We selected data from 1) the National Alzheimer's Coordinating Center: a total of 3,486 AD cases and 4,511 controls (N = 7,997, 60% female) with genotypes from the Alzhei

Ранние и поздние нейропатологические особенности менингоэнцефалита, связанного с вирусом Мараба.

Вирус Мараба является частью рода Везукуловирус семьи Рабдовиридае, который был изолирован в 1983 году от песчаников, захваченных в муниципалитете Мараба, штат Пара, Амацониа, Бразилия. Несмотря на то, что прошло 30 лет после его изоляции, мало что известно о нейропатологии, вызванной вирусом Мараба. В соответствии с этим в этом исследовании были проанализированы гистопатологические особенности, подстрекательские глиальные изменения, концентрации цитокина и активность окиси азота в энцфалоне взрослых мышей, подвергшихся вирусной ностральной инфекции в Марабе. Результаты показали, что через 6 д

Совпадение в аннотации оригинала
Maraba virus is a member of the genus Vesiculovirus of the Rhabdoviridae family that was isolated in 1983 from sandflies captured in the municipality of Maraba, state of Pará, Amazônia, Brazil. Despite 30 years having passed since its isolation, little is known about the neuropathology induced by the Maraba virus. Accordingly, in this study the histopatholog…

Neuropathology and diagnostic features of rabies in a litter of piglets, with a brief review of the literature.

Porcine rabies is exceedingly rare worldwide. We describe herein the neuropathology and the diagnostic features of an outbreak of rabies in a litter of piglets attacked by a skunk in Georgia, United States. Rabies viral infection was confirmed in 2 of 3 piglets submitted for testing. Inflammatory and degenerative changes were more prominent in the brainstem and consisted of lymphoplasmacytic meningoencephalitis with glial nodules, neuronal necrosis, and neuronophagia. No viral inclusions (Negri bodies) were observed in multiple sections of brain. A fluorescent antibody test on fresh samples of…

Neuropathological correlates and genetic architecture of microglial activation in elderly human brain.

Microglia, the resident immune cells of the brain, have important roles in brain health. However, little is known about the regulation and consequences of microglial activation in the aging human brain. Here we report that the proportion of morphologically activated microglia (PAM) in postmortem cortical tissue is strongly associated with β-amyloid, tau-related neuropathology, and the rate of cognitive decline. Effect sizes for PAM measures are substantial, comparable to that of APOE ε4, the strongest genetic risk factor for Alzheimer's disease, and mediation models support an upstream role fo…

Clinical and neuropathologic analysis of intracerebral hemorrhage in patients with cerebral amyloid angiopathy.

OBJECTIVE: To evaluate the clinical and histopathological features of elderly patients with subcortical intracerebral hemorrhage (ICH), and to analyze the presence of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) type pathologic changes using amyloid beta (Aβ) and tau immunohistochemistry. PATIENTS AND METHODS: We retrospectively analyzed cases satisfying the Boston criteria for CAA among patients with subcortical hemorrhage who underwent surgical removal by craniotomy at our hospital. Surgical specimens were subjected to hematoxylin and eosin (HE) staining as well as immunos

The neuropathological study of myelin oligodendrocyte glycoprotein in the temporal lobe of schizophrenia patients.

OBJECTIVE: Recent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients. METHODS: Myelin oligodendrocyte gl

A Japanese Family of Spinocerebellar Ataxia Type 21: Clinical and Neuropathological Studies.

Spinocerebellar ataxia type 21 (SCA21) is a rare subtype of autosomal dominant cerebellar ataxias, which was first identified in a French family and has been reported almost exclusively in French ancestry so far. We here report the first Japanese family with SCA21, in which all affected members examined carried a heterozygous c.509C > T:p.Pro170Leu variant in TMEM240. Their clinical features were summarized as a slowly progressive ataxia of young-adult onset (5-48 years) associated with various degree of psychomotor retardation or cognitive impairment. The MR images revealed atrophy in the cer