Both N-terminal and C-terminal fragments of Presenilin 1 colocalize with neurofibrillary tangles in neurons and dystrophic neurites of senile plaques in Alzheimer's disease

1998 ◽  
Vol 53 (1) ◽  
pp. 99-106 ◽  
Author(s):  
De-Hua Chui ◽  
Keiro Shirotani ◽  
Hiroshi Tanahashi ◽  
Haruhiko Akiyama ◽  
Kazuharu Ozawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Senile Plaques ◽  
Presenilin 1 ◽  
Dystrophic Neurites

scholarly journals NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Mariana Van Zeller ◽  
Diogo M. Dias ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Nlrp3 Inflammasome ◽  
Neuronal Death ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

scholarly journals Diagnostic utility of quantitating neurofilament-immunoreactive Alzheimer's disease lesions.

1994 ◽  
Vol 42 (12) ◽  
pp. 1625-1634 ◽  
Author(s):  
S M de la Monte ◽  
J R Wands
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Monoclonal Antibodies ◽  
Neurofibrillary Tangles ◽  
Paired Helical Filament ◽  
Dystrophic Neurites ◽  
Associated Lesions ◽  
End Stage

The diagnosis of Alzheimer's disease (AD) neurodegeneration is based on histopathological detection of paired helical filament-associated lesions. Silver stains are routinely used but the results are fraught with intra- and interinstitutional variability. This study employed monoclonal antibodies to middle and high molecular weight neurofilament subunits in an immunohistochemical assay to assess the extent of paired helical filament-associated lesions in brains with AD, Down's syndrome plus AD lesions (AD+DN), Parkinson's disease dementia (PD), AD+PD, and normal aging changes. The densities of neurofilament-immunoreactive (NFI) cortical neurofibrillary tangles and plaques were significantly higher in AD and AD+DN than in PD and aged control brains (p < 0.001), and NFI neurofibrillary tangles and plaques were more abundant in AD and AD+DN compared with AD+PD and PD, yet all patients with AD, AD+PD, or PD died with end-stage dementia. In contrast, the densities of NFI dystrophic neurites (primarily dendrites) in cortical Layer 2 were similar among the AD, AD+DN, AD+PD, and PD groups, and all were significantly higher than control (p < 0.005). Stepwise multivariate regression analysis demonstrated significant correlations between AD diagnosis and high densities of NFI neurofibrillary tangles and plaques (p < 0.001) and between end-stage AD-type dementia and high densities of NFI dystrophic neurites (p < 0.001). This study demonstrates that the histopathological lesions correlated with AD dementia can be readily detected and quantified by immunostaining with monoclonal antibodies to phosphorylated and non-phosphorylated neurofilaments. Moreover, the findings suggest that NFI neurite pathology may be an important feature contributing to the clinically manifested AD-type dementia in individuals with Parkinson's disease.

A topographical study of senile plaques and neurofibrillary tangles in the hippocampi of patients with Alzheimer's disease and cognitively impaired patients with schizophrenia

1993 ◽  
Vol 49 (1) ◽  
pp. 41-62 ◽  
Author(s):  
Manuel F. Casanova ◽  
Nicholas W. Carosella ◽  
James M. Gold ◽  
Joel E. Kleinman ◽  
Daniel R. Weinberger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Senile Plaques ◽  
Cognitively Impaired

scholarly journals The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Troy T. Rohn
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Senile Plaques ◽  
Myeloid Cells ◽  
Disease Process ◽  
Age Related

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.

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