Is Alzheimer's disease an inflammasomopathy?

Ageing Res Rev

CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculty of Medicine, Polo I, 1st Floor, 3004-504, Coimbra, Portugal; CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Rua Larga, Faculty of Medicine, Polo I, 1st Floor, 3004-504, Coimbra, Portugal; Faculty of Pharmacy, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal. Electronic address:

Published: December 2019

Alzheimer's disease (AD) is the most common form of dementia in the elderly and, despite the tremendous efforts researchers have put into AD research, there are no effective options for prevention and treatment of the disease. The best way to reach this goal is to clarify the mechanisms involved in the onset and progression of AD. In the last few years the views about the drivers of AD have been changing and nowadays it is believed that neuroinflammation takes center stage in disease pathogenesis. Herein, we provide an overview about the role of neuroinflammation in AD describing the role of microglia and astroglia is this process. Then, we will debate the NLRP3 inflammasome putting the focus on its activation through the canonical, non-canonical and alternative pathways and the triggers involved herein namely endoplasmic reticulum stress, mitochondrial dysfunction, reactive oxygen species and amyloid β peptide. Data supporting the hypothesis that inflammasome-mediated peripheral inflammation may contribute to AD pathology will be presented. Finally, a brief discussion about the therapeutic potential of NLRP3 inflammasome modulation is also provided.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arr.2019.100966DOI Listing

Publication Analysis

Top Keywords

alzheimer's disease
8
nlrp3 inflammasome
8
disease inflammasomopathy?
4
inflammasomopathy? alzheimer's
4
disease common
4
common form
4
form dementia
4
dementia elderly
4
elderly despite
4
despite tremendous
4

Similar Publications

Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls.

View Article and Find Full Text PDF

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue.

View Article and Find Full Text PDF

Introduction: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses.

Methods: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease ( = 18), non-Alzheimer's disease neurodegeneration ( = 23) or primary psychiatric disorders ( = 24).

View Article and Find Full Text PDF

Background: Effective detection of cognitive impairment in the primary care setting is limited by lack of time and specialized expertise to conduct detailed objective cognitive testing and few well-validated cognitive screening instruments that can be administered and evaluated quickly without expert supervision. We therefore developed a model cognitive screening program to provide relatively brief, objective assessment of a geriatric patient's memory and other cognitive abilities in cases where the primary care physician suspects but is unsure of the presence of a deficit.

Methods: Referred patients were tested during a 40-min session by a psychometrist or trained nurse in the clinic on a brief battery of neuropsychological tests that assessed multiple cognitive domains.

View Article and Find Full Text PDF

Want 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!