Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19.

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters.

alleles modulate inflammation during microbial infection of mice in a sex-dependent manner.

Variants in the leucine-rich repeat kinase-2 () gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested this hypothesis in two ways.

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.

Holocranohistochemistry enables the visualization of α-synuclein expression in the murine olfactory system and discovery of its systemic anti-microbial effects.

Braak and Del Tredici have proposed that typical Parkinson disease (PD) has its origins in the olfactory bulb and gastrointestinal tract. However, the role of the olfactory system has insufficiently been explored in the pathogeneses of PD and Alzheimer disease (AD) in laboratory models. Here, we demonstrate applications of a new method to process mouse heads for microscopy by sectioning, mounting, and staining whole skulls ('holocranohistochemistry').

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies.

Radiological and pathological features associated with IDH1-R132H mutation status and early mortality in newly diagnosed anaplastic astrocytic tumours.

Background: Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality.

Striatal blood-brain barrier permeability in Parkinson's disease.

In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD). However, these have lacked either anatomic definition or the ability to recognize minute changes in BBB integrity. Here, using histologic markers of serum protein, iron, and erythrocyte extravasation, we have shown significantly increased permeability of the BBB in the postcommissural putamen of PD patients.

Hypothesis: a role for EBV-induced molecular mimicry in Parkinson's disease.

Current concepts regarding the pathogenesis of Parkinson's disease support a model whereby environmental factors conspire with a permissive genetic background to initiate the disease. The identity of the responsible environmental trigger has remained elusive. There is incontrovertible evidence that aggregation of the neuronal protein alpha-synuclein is central to disease pathogenesis.

Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.

Parkinson's disease is characterized by the pathological aggregation of Alpha-synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of α-synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of α-synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade.

Depletion of intranuclear rodlets in mouse models of diabetes.

Intranuclear rodlets (INRs) are structures present within the nuclei of human insulin-secreting beta cells of the endocrine pancreas. Their physiological significance, and whether they are altered in disease, is unknown. In the present study, the proportion of pancreatic beta cells containing INRs was examined in mouse models of type II diabetes and in a model with improved beta cell function.

The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1 phosphorylation in neuronal death.

Accumulating evidence suggests that deregulated cyclin-dependent kinase 5 (Cdk5) plays a critical part in neuronal death. However, the pathogenic targets of Cdk5 are not fully defined. Here we demonstrate that the Cdk5 activator p35 interacts directly with apurinic/apyrimidinic endonuclease 1 (Ape1), a protein crucial for base excision repair (BER) following DNA damage.

Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease.

We reported previously that calpain-mediated Cdk5 activation is critical for mitochondrial toxin-induced dopaminergic death. Here, we report a target that mediates this loss. Prx2, an antioxidant enzyme, binds Cdk5/p35.

MPTP induces intranuclear rodlet formation in midbrain dopaminergic neurons.

Neuronal intranuclear rodlets (INRs; rodlets of Roncoroni) have been known to neuroanatomists since the turn of the century. However, the functional and/or pathological significance of these structures has remained enigmatic. We recently demonstrated that these structures are immunoreactive for class III beta tubulin and for glucocorticoid receptor.

Acute myocardial infarction in a young man with dilated cardiomyopathy: clinicopathological correlation.

Cardiac involvement is commonly described in autopsy examinations of patients infected with human immunodeficiency virus (HIV). However, only a small percentage have clinically significant cardiac disease. Dilated cardiomyopathy is one of the most common HIV-related heart diseases.

Reduction of neuronal intranuclear rodlets immunoreactive for tubulin and glucocorticoid receptor in Alzheimer's disease.

Neuronal intranuclear rodlets were described in normal brain over a century ago, but their functional significance and pathological relevance is unknown. Here, we show co-localization of tubulin and glucocorticoid receptor-like immunoreactivity in these intranuclear inclusions in human brain. In addition, we provide evidence for a massive reduction in their areal density in Alzheimer's disease brain, but not in another common neurodegenerative condition, dementia with Lewy bodies.