post-mortem alzheimers disease autophage

INTRODUCTION: Tau phosphorylated at threonine-217 (pT217-tau) is a novel fluid-based biomarker that predicts onset of Alzheimer's disease (AD) symptoms, but little is known about how pT217-tau arises in the brain, as soluble pT217-tau is dephosphorylated post mortem in humans. METHODS: We used multilabel immunofluorescence and immunoelectron microscopy to examine the subcellular localization of early-stage pT217-tau in entorhinal and prefrontal cortices of aged macaques with naturally occurring tau pathology and assayed pT217-tau levels in plasma...

BACKGROUND: The growing prevalence of Alzheimer's disease (AD) is becoming a global health challenge without effective treatments. Defective mitochondrial function and mitophagy have recently been suggested as etiological factors in AD, in association with abnormalities in components of the autophagic machinery like lysosomes and phagosomes. Several large transcriptomic studies have been performed on different brain regions from AD and healthy patients, and their data represent a vast source of important information that can be utilized to understand this condition...

INTRODUCTION: Growing evidence supports that dysfunctional autophagy, the major cell mechanism responsible for removing protein aggregates and a route of clearance for Tau in healthy neurons, is a major finding in demented Alzheimer's disease (AD) patients. However, the association of autophagy with maintenance of cognitive integrity in resilient individuals who have AD neuropathology but remain non-demented (NDAN) has not been evaluated. METHODS: Using post mortem brain samples from age-matched healthy control, AD, and NDAN subjects, we evaluated autophagy in relation to Tau pathology using Western blot, immunofluorescence and RNA-seq...

Since the 1960s viral pathogenesis researchers have considered herpesviruses as an underlying factor for Alzheimer's disease (AD). We reported molecular interactions between herpes simplex virus type 1 (HSV-1) and the amyloid precursor protein (APP), the parent of amyloid plaques pathognomonic for AD (Sapute-Krishnan et al., 2003 and 2006; Chen et al., 2011, Bearer and Wu, 2019). Furthermore, others report biochemical interactions between HSV-1 and autophagy. Using several brain banks for specimens of four brain regions in post-mortems of individuals with and without cognitive impairment prior to death...

BACKGROUND: Microglia-mediated neuroinflammation is hypothesized to contribute to disease progression in neurodegenerative diseases such as Alzheimer's Disease (AD). Recent single-cell RNA-seq studies highlight the heterogeneity of microglial subtypes. Since microglia are a relatively small proportion of CNS cells, standard single-cell omics approaches do not fully capture the diversity of microglia in human subjects. Understanding the gene expression and regulatory networks which define the spectrum of microglia phenotypes is critical to identifying specific targets for neuroinflammation modulating therapies...

BACKGROUND: Microglia-mediated neuroinflammation is hypothesized to contribute to disease progression in neurodegenerative diseases such as Alzheimer's Disease (AD). Microglia subtypes are complex, with beneficial and harmful phenotypes. Understanding the gene expression networks which define the spectrum of microglia phenotypes is critical to identifying specific targets for neuroinflammation modulating therapies. METHOD: Our study utilized post-mortem brain tissue from 22 total (7 male) participants; 12 (3 male) had significant AD neuropathic change...

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. In this sense, synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease. At the histopathological level, post mortem AD brains typically exhibit intraneuronal neurofibrillary tangles (NFTs) along with the accumulation of amyloid-beta (Abeta) peptides in the form of extracellular deposits...

INTRODUCTION: The accumulation of insoluble proteins within neurons and glia cells is a pathological hallmark of several neurodegenerative diseases. Abnormal aggregation of the microtubule-associated protein tau characterizes the neuropathology of tauopathies, such as Alzheimer disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). An impairment of the lysosomal degradation pathway called macroautophagy, hereafter referred to as autophagy, could contribute to the accumulation of aggregated proteins...

Protein inclusions in neurodegenerative diseases are associated with p62, which has an important role in autophagic clearance of polyubiquitinated proteins. Selective autophagy is regulated by S403-phosphorylation of p62, and S403-phosphorylated p62 (S403-phos-p62) accumulates in Atg5 conditional knockout (Atg5CKO) mice in which autophagosome formation is impaired. We performed immunohistochemical tests for the presence of S403-phos-p62 in postmortem brain of neurodegenerative disease cases, and found accumulations in amyotrophic lateral sclerosis and Alzheimer's disease tissues...

Abnormally hyperphosphorylated tau aggregates form paired helical filaments (PHFs) in neurofibrillary tangles, a key hallmark of Alzheimer's disease (AD) and other tauopathies. The cerebrospinal fluid (CSF) levels of soluble total tau and phospho-tau from clinically diagnosed AD patients are significantly higher compared with controls. Data from both in vitro and in vivo AD models have implied that an aberrant increase of mammalian target of rapamycin (mTor) signaling may be a causative factor for the formation of abnormally hyperphosphorylated tau...

AIMS: Granulovacuolar degeneration involves the accumulation of large, double membrane-bound bodies within certain neurones during the course of Alzheimer's disease (AD) and other adult-onset dementias. Because of the two-layer membrane morphology, it has been proposed that the bodies are related to autophagic organelles. The aim of this study was to test this hypothesis, and determine the approximate stage at which the pathway stalls in AD. METHODS: Spatial colocalization of autophagic and endocytic markers with casein kinase 1 delta, a marker for granulovacuolar degeneration (GVD) bodies, was evaluated in hippocampal sections prepared from post mortem Braak stage IV and V AD cases using double-label confocal fluorescence microscopy...