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.
Results: GVD bodies colocalized weakly with early-stage autophagy markers LC3 and p62, but strongly with late-stage marker lysosome-associated membrane protein 1 (LAMP1), which decorated their surrounding membranes. GVD bodies also colocalized strongly with charged multivesicular body protein 2B (CHMP2B), which colocalized with the core granule, but less strongly with lysosomal marker cathepsin D.
Conclusions: The resultant immunohistochemical signature suggests that granulovacuolar degeneration bodies (GVBs) do contain late-stage autophagic markers, and accumulate at the nexus of autophagic and endocytic pathways. The data further suggest that failure to complete autolysosome formation may be an important correlate of GVB accumulation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037976 | PMC |
| http://dx.doi.org/10.1111/j.1365-2990.2010.01135.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of an Alzheimer's disease-associated form of necroptosis rescues neuronal death in mouse models.
Sci Transl Med
October 2024
Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven, Leuven Brain Institute (LBI), Leuven, Belgium.
Necroptosis is a regulated form of cell death that has been observed in Alzheimer's disease (AD) along with the classical pathological hallmark lesions of amyloid plaques and Tau neurofibrillary tangles. To understand the neurodegenerative process in AD, we studied the role of necroptosis in mouse models and primary mouse neurons. Using immunohistochemistry, we demonstrated activated necroptosis-related proteins in transgenic mice developing Tau pathology and in primary neurons from amyloid precursor protein (APP)-Tau double transgenic mice treated with phosphorylated Tau seeds derived from a patient with AD but not in APP transgenic mice that only exhibited β-amyloid deposits.
View Article and Find Full Text PDFIncreased expression of the proapoptotic presenilin associated protein is involved in neuronal tangle formation in human brain.
Sci Rep
October 2024
Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China.
Article Synopsis
- * In AD-affected brains, PSAP levels are higher and correlate with neurodegenerative markers like pTau and Amyloid tangles, suggesting a role in tangle formation.
- * The study also found that in aged mice models of AD, PSAP expression remained similar to that in healthy mice, indicating a complex relationship between PSAP and aging in the context of neurodegenerative diseases.
Hypothesis-based investigation of known AD risk variants reveals the genetic underpinnings of neuropathological lesions observed in Alzheimer's-type dementia.
Acta Neuropathol
October 2024
Complex Genetics of Alzheimer's Disease Group, VIB-UAntwerp Center for Molecular Neurology, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610, Antwerp, Belgium.
Alzheimer's disease (AD) is the leading cause of dementia worldwide. Besides neurofibrillary tangles and amyloid beta (Aβ) plaques, a wide range of co-morbid neuropathological features can be observed in AD brains. Since AD has a very strong genetic background and displays a wide phenotypic heterogeneity, this study aims at investigating the genetic underpinnings of co-morbid and hallmark neuropathological lesions.
View Article and Find Full Text PDFThe necroptosis cell death pathway drives neurodegeneration in Alzheimer's disease.
Acta Neuropathol
June 2024
Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, 3000, Leuven, Belgium.
Although apoptosis, pyroptosis, and ferroptosis have been implicated in AD, none fully explains the extensive neuronal loss observed in AD brains. Recent evidence shows that necroptosis is abundant in AD, that necroptosis is closely linked to the appearance of Tau pathology, and that necroptosis markers accumulate in granulovacuolar neurodegeneration vesicles (GVD). We review here the neuron-specific activation of the granulovacuolar mediated neuronal-necroptosis pathway, the potential AD-relevant triggers upstream of this pathway, and the interaction of the necrosome with the endo-lysosomal pathway, possibly providing links to Tau pathology.
View Article and Find Full Text PDFNeuroinflammatory Responses Occur in Brain Lesions During Alzheimer's Disease: Postmortem Case Report.
J Alzheimers Dis
February 2024
Cytokines and NO-Synthases, Immunity and Pathogenesis Team, Laboratory of Cellular and Molecular Biology, Faculty of Biological Science, University of Sciences and Technology Houari Boumediene, Algiers, Algeria.
Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. It is characterized by a gradual decrease in cognitive function and is considered a disorder in which the intensifying neuronal loss. The autopsy is considered the gold standard for the diagnosis of AD and non-AD dementia.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!