scholarly journals Activation of CREB‐mediated autophagy by thioperamide ameliorates β‐amyloid pathology and cognition in Alzheimer’s disease

Aging Cell ◽  
2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Jiangong Wang ◽  
Bin Liu ◽  
Yong Xu ◽  
Meizi Yang ◽  
Chaoyun Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pathology ◽  
Β Amyloid

scholarly journals Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits

2018 ◽  
Author(s):  
Ana Belen Lopez-Rodriguez ◽  
Edel Hennessy ◽  
Carol Murray ◽  
Anouchka Lewis ◽  
Niamh de Barra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Inflammasome Activation ◽  
Nuclear Localisation ◽  
Amyloid Pathology ◽  
Model Of Alzheimer’S Disease ◽  
Nlrp3 Inflammasome Activation ◽  
Β Amyloid ◽  
Secondary Stimulation

AbstractAlzheimer’s disease (AD) causes devastating cognitive decline and has no disease-modifying therapies. Neuroinflammation is a significant contributor to disease progression but its precise contribution remains unclear. An emerging literature indicates that secondary inflammatory insults including acute trauma and infection alter the trajectory of chronic neurodegenerative diseases and the roles of microglia and astrocytes require elucidation. The current study, using the APP/PS1 mouse model of AD, demonstrates that microglia are primed by β-amyloid pathology to induce exaggerated IL-1β responses to acute stimulation with LPS or IL-1β. Despite disease-associated NLRP3 inflammasome activation, evidenced by ASC speck formation, APP/PS1 microglial cells show neither IL-1β induction nor NFκB p65 nuclear localisation. Upon secondary stimulation with LPS or IL-1β, NFκB-p65 nuclear localisation and exaggerated pro-IL-1 induction occur. Microglial priming was also unmasked by secondary stimulation with systemic LPS leading to significant cognitive impairment in APP/PS1 mice compared to WT LPS-treated mice. Astrocytes have also recently emerged as displaying significant phenotypic heterogeneity. Here, by-passing microglial priming, and acutely challenging mice with intra-hippocampal IL-1β we demonstrate that astrocytes proximal to Aβ-plaques are also primed to produce exaggerated CCL2, CXCL1 and CXCL10 responses. Many astrocytosis-associated genes in APP/PS1 mice share these exaggerated responses to IL-1β, while others are equally induced in both strains. Collectively the data show that the amyloid-laden brain shows multiple vulnerabilities to secondary inflammatory challenge: both microglia and astrocytes are primed to produce exaggerated secondary inflammation and systemic LPS is sufficient to cause cognitive impairments relevant to delirium, selectively in animals with prior amyloid pathology.

β-Amyloid pathology in the entorhinal cortex of rats induces memory deficits: Implications for Alzheimer’s disease

Neuroscience ◽  
2007 ◽  
Vol 147 (1) ◽  
pp. 28-36 ◽  
Author(s):  
E. Sipos ◽  
A. Kurunczi ◽  
Á. Kasza ◽  
J. Horváth ◽  
K. Felszeghy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Memory Deficits ◽  
Amyloid Pathology ◽  
Β Amyloid

scholarly journals CSF β-amyloid and white matter damage: a new perspective on Alzheimer’s disease

2017 ◽  
Vol 89 (4) ◽  
pp. 352-357 ◽  
Author(s):  
Anna M Pietroboni ◽  
Marta Scarioni ◽  
Tiziana Carandini ◽  
Paola Basilico ◽  
Marcello Cadioli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Statistical Tests ◽  
Brain Mri ◽  
Healthy Controls ◽  
Microstructural Damage ◽  
Amyloid Pathology ◽  
Apparent Diffusion Coefficient Value ◽  
Β Amyloid

ObjectiveTo assess the connection between amyloid pathology and white matter (WM) macrostructural and microstructural damage in demented patients compared with controls.MethodsEighty-five participants were recruited: 65 with newly diagnosed Alzheimer’s disease (AD), non-AD dementia or mild cognitive impairment and 20 age-matched and sex-matched healthy controls. β-amyloid1-42 (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF Aβ levels (Aβ(+)), while 23 had normal CSF Aβ levels (Aβ(−)). All participants underwent neurological examination, neuropsychological testing and brain MRI. We used T2-weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses.ResultsWe found an increased WM-LL in Aβ(+) compared with both, healthy controls (p=0.003) and Aβ(−) patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients’ WM-LL (r=−0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient value was higher in all patients than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In Aβ(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001).ConclusionsWM damage is crucial in AD pathogenesis. The correlation between CSF Aβ levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.

scholarly journals Characterization of a Novel Mouse Model of Alzheimer’s Disease—Amyloid Pathology and Unique β-Amyloid Oligomer Profile

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126317 ◽  
Author(s):  
Peng Liu ◽  
Jennifer B. Paulson ◽  
Colleen L. Forster ◽  
Samantha L. Shapiro ◽  
Karen H. Ashe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Pathology ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid ◽  
Amyloid Oligomer
Sign in / Sign up

Export Citation Format

Share Document