Acta Neuropathologica: Proteomics study of empty bubble degeneration of Alzheimer's particles and entanglement of neurogenic fibers

In addition to amyloid plaques and neurogenic fiber tangles (NFTs), the pathological characteristics of Alzheimer's disease (AD) are usually neurons with particle empty bubble degeneration (GVD).
GVD is represented in standard Sumu fine dyeing as an edge bubble with a diameter of up to 5 m, which contains a dense core.
these GVD small bodies were initially found mainly in the hema CA1 region, the CA2 region and the lower hypoclyceral cone neurons.
later in AD, GVD also appeared in other brain regions, such as the temporal lobe, the lower thalium and the amygdala.
GVD is a common feature of AD.
GVD is closely related to the occurrence of NFTs, GVD is even considered to be a pre-NFT stage in the onset of AD.
, the composition of the GVD body, the mechanisms associated with GVD, and the exact relationship between GVD and NFTs are not clear.
this study used a combination of immunobiobiochemistry (IHC) and laser microcution (LMD) to isolate GVD neurons and tangled neurons from the sea mass (n-12) after the death of AD patients using the typical markers casein kinase (CK) 1 and phosphorylation tau (AT8).
used the same method to isolate control neurons (n-12) from cases of cognitive health.
the study used the unmarked LC-MS/MS method to analyze the proteomics of 3,000 neurons in each sample.
, a total of 2,596 proteins were quantified in the sample, and the researchers observed significant changes in the abundance of 197 of the 115 proteins in GVD and 197 proteins in tangled neurons compared to the control neuron group.
addition, IHC confirms the presence of PPA, TOMM34, HSP70, CHMP1A, TPPP, and VXN in GVD neurons.
also found a variety of proteins specific to GVD small bodies, of which VXN and TOMM34 are the most prominent new protein markers of GVD small bodies.
overall, changes in proteomics associated with protein folding, protease function, lysosome pathways, micro-tube and cytostelete-related functions, RNA processing, and glycolysis were found in GVD neurons.
addition to these proteomics, entangled neurons show a decrease in kerucleal proteins and various proteins associated with protein folding.
study was the first to provide a comprehensive quantitative assessment of the protein abundance of GVD and entangled neurons.
is consistent with the functional data of the previous tau pathology-induced GVD, the data in this study support that GVD is a model of the pre-NFT phase, which represents the stage of protein balance and the destruction of in-cell environmental stability.
the molecular mechanism and cellular process of GVD and its relationship with tau pathology, which is of great significance for finding new therapeutic targets.
Hondius, D.C., Koopmans, F., Leistner, C. et al. The proteome of granulovacuolar degeneration and neurofibrillary tangles in Alzheimer’s disease. Acta Neuropathol 141, 341–358 (2021). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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