scholarly journals Re-examining tau-immunoreactive pathology in the population: granulovacuolar degeneration and neurofibrillary tangles

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Sally Hunter ◽  
◽  
Thais Minett ◽  
Tuomo Polvikoski ◽  
Elizabeta Mukaetova-Ladinska ◽  
...  
Keyword(s):  
Neurofibrillary Tangles ◽  
Granulovacuolar Degeneration

scholarly journals Lysosomal Fusion Dysfunction as a Unifying Hypothesis for Alzheimer's Disease Pathology

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Kristen E. Funk ◽  
Jeff Kuret
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Neurofibrillary Tangles ◽  
Recent Literature ◽  
Senile Plaques ◽  
Disease Onset ◽  
Granulovacuolar Degeneration

Alzheimer's disease is characterized pathologically by extracellular senile plaques, intracellular neurofibrillary tangles, and granulovacuolar degeneration. It has been debated whether these hallmark lesions are markers or mediators of disease progression, and numerous paradigms have been proposed to explain the appearance of each lesion individually. However, the unfaltering predictability of these lesions suggests a single pathological nidus central to disease onset and progression. One of the earliest pathologies observed in Alzheimer's disease is endocytic dysfunction. Here we review the recent literature of endocytic dysfunction with particular focus on disrupted lysosomal fusion and propose it as a unifying hypothesis for the three most-studied lesions of Alzheimer's disease.

scholarly journals Changes in the ageing brain in health and disease

1997 ◽  
Vol 352 (1363) ◽  
pp. 1781-1792 ◽  
Author(s):  
Brian H. Anderton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Senile Plaques ◽  
Brain Regions ◽  
Granulovacuolar Degeneration ◽  
Hirano Bodies ◽  
Age Related ◽  
Brain Ageing ◽  
Ageing Brain

The brains of individuals, who are cognitively normal, show age–related changes that include an overall reduction in brain volume and weight, which are associated with gyral atrophy and widening of the sulci of the cerebral cortex, and enlargement of the brain ventricles. These changes are partly the result of nerve cell loss but accurate estimates of neuronal loss are notoriously difficult to make. Microscopically, there are increasing amounts of the age–related pigment, lipofuscin, granulovacuolar degeneration in neurons, Hirano bodies, variable amounts of diffuse deposits of β–amyloid in the parenchyma, the presence of neurofibrillary tangles mainly confined to the hippocampus and amygdala, and sparse numbers of senile plaques in these brain regions and also in other cortical areas. Of these changes, neurofibrillary tangles and senile plaques are the neuropathological hallmark of Alzheimer's disease in which they are more abundant and widespread. Alzheimer's disease has therefore been regarded as accelerated brain ageing; however, the realization that there is a strong genetic contribution to developing the disease at least implies that it may not be the inevitable, even if frequent, consequence of old age. Understanding the molecular basis of plaque and tangle formation is advancing greatly and is the main focus of research into the cellular and molecular changes observed in the ageing brain.

scholarly journals Phosphatidylinositol‐4,5‐bisphosphate is enriched in granulovacuolar degeneration bodies and neurofibrillary tangles

2014 ◽  
Vol 40 (4) ◽  
pp. 489-501 ◽  
Author(s):  
Tomokazu Nishikawa ◽  
Tetsuya Takahashi ◽  
Masahiro Nakamori ◽  
Yu Yamazaki ◽  
Takashi Kurashige ◽  
...  
Keyword(s):  
Neurofibrillary Tangles ◽  
Granulovacuolar Degeneration ◽  
Granulovacuolar Degeneration Bodies

scholarly journals The proteome of granulovacuolar degeneration and neurofibrillary tangles in Alzheimer’s disease

2021 ◽  
Vol 141 (3) ◽  
pp. 341-358
Author(s):  
David C. Hondius ◽  
Frank Koopmans ◽  
Conny Leistner ◽  
Débora Pita-Illobre ◽  
Regina M. Peferoen-Baert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Folding ◽  
Neurofibrillary Tangles ◽  
Ribosomal Proteins ◽  
Molecular Mechanisms ◽  
Disease Process ◽  
Protein Markers ◽  
Granulovacuolar Degeneration ◽  
Tau Pathology

AbstractGranulovacuolar degeneration (GVD) is a common feature in Alzheimer’s disease (AD). The occurrence of GVD is closely associated with that of neurofibrillary tangles (NFTs) and GVD is even considered to be a pre-NFT stage in the disease process of AD. Currently, the composition of GVD bodies, the mechanisms associated with GVD and how GVD exactly relates to NFTs is not well understood. By combining immunohistochemistry (IHC) and laser microdissection (LMD) we isolated neurons with GVD and those bearing tangles separately from human post-mortem AD hippocampus (n = 12) using their typical markers casein kinase (CK)1δ and phosphorylated tau (AT8). Control neurons were isolated from cognitively healthy cases (n = 12). 3000 neurons per sample were used for proteome analysis by label free LC–MS/MS. In total 2596 proteins were quantified across samples and a significant change in abundance of 115 proteins in GVD and 197 in tangle bearing neurons was observed compared to control neurons. With IHC the presence of PPIA, TOMM34, HSP70, CHMP1A, TPPP and VXN was confirmed in GVD containing neurons. We found multiple proteins localizing specifically to the GVD bodies, with VXN and TOMM34 being the most prominent new protein markers for GVD bodies. In general, protein groups related to protein folding, proteasomal function, the endolysosomal pathway, microtubule and cytoskeletal related function, RNA processing and glycolysis were found to be changed in GVD neurons. In addition to these protein groups, tangle bearing neurons show a decrease in ribosomal proteins, as well as in various proteins related to protein folding. This study, for the first time, provides a comprehensive human based quantitative assessment of protein abundances in GVD and tangle bearing neurons. In line with previous functional data showing that tau pathology induces GVD, our data support the model that GVD is part of a pre-NFT stage representing a phase in which proteostasis and cellular homeostasis is disrupted. Elucidating the molecular mechanisms and cellular processes affected in GVD and its relation to the presence of tau pathology is highly relevant for the identification of new drug targets for therapy.

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