scholarly journals Mitochondrial Amyloid-β Levels are Associated with the Extent of Mitochondrial Dysfunction in Different Brain Regions and the Degree of Cognitive Impairment in Alzheimer's Transgenic Mice

2010 ◽  
Vol 20 (s2) ◽  
pp. S535-S550 ◽  
Author(s):  
Natasa Dragicevic ◽  
Malgorzata Mamcarz ◽  
Yuyan Zhu ◽  
Robert Buzzeo ◽  
Jun Tan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Transgenic Mice ◽  
Mitochondrial Dysfunction ◽  
Amyloid Β ◽  
Brain Regions

scholarly journals Interleukin-1β mediates alterations in mitochondrial fusion/fission proteins and memory impairment induced by amyloid-β oligomers

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Andre F. Batista ◽  
Tayná Rody ◽  
Leticia Forny-Germano ◽  
Suzana Cerdeiro ◽  
Maria Bellio ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mitochondrial Dysfunction ◽  
Memory Impairment ◽  
Mitochondrial Dynamics ◽  
Interleukin 1 ◽  
Amyloid Β ◽  
Mitochondrial Fusion ◽  
Synapse Loss ◽  
Cynomolgus Macaques ◽  
The Impact

Abstract Background The lack of effective treatments for Alzheimer’s disease (AD) reflects an incomplete understanding of disease mechanisms. Alterations in proteins involved in mitochondrial dynamics, an essential process for mitochondrial integrity and function, have been reported in AD brains. Impaired mitochondrial dynamics causes mitochondrial dysfunction and has been associated with cognitive impairment in AD. Here, we investigated a possible link between pro-inflammatory interleukin-1 (IL-1), mitochondrial dysfunction, and cognitive impairment in AD models. Methods We exposed primary hippocampal cell cultures to amyloid-β oligomers (AβOs) and carried out AβO infusions into the lateral cerebral ventricle of cynomolgus macaques to assess the impact of AβOs on proteins that regulate mitochondrial dynamics. Where indicated, primary cultures were pre-treated with mitochondrial division inhibitor 1 (mdivi-1), or with anakinra, a recombinant interleukin-1 receptor (IL-1R) antagonist used in the treatment of rheumatoid arthritis. Cognitive impairment was investigated in C57BL/6 mice that received an intracerebroventricular (i.c.v.) infusion of AβOs in the presence or absence of mdivi-1. To assess the role of interleukin-1 beta (IL-1β) in AβO-induced alterations in mitochondrial proteins and memory impairment, interleukin receptor-1 knockout (Il1r1−/−) mice received an i.c.v. infusion of AβOs. Results We report that anakinra prevented AβO-induced alteration in mitochondrial dynamics proteins in primary hippocampal cultures. Altered levels of proteins involved in mitochondrial fusion and fission were observed in the brains of cynomolgus macaques that received i.c.v. infusions of AβOs. The mitochondrial fission inhibitor, mdivi-1, alleviated synapse loss and cognitive impairment induced by AβOs in mice. In addition, AβOs failed to cause alterations in expression of mitochondrial dynamics proteins or memory impairment in Il1r1−/− mice. Conclusion These findings indicate that IL-1β mediates the impact of AβOs on proteins involved in mitochondrial dynamics and that strategies aimed to prevent pathological alterations in those proteins may counteract synapse loss and cognitive impairment in AD.

O3-01-01: Amyloid-β protofibrils are linked to cognitive impairment in Alzheimer's disease transgenic mice

2008 ◽  
Vol 4 ◽  
pp. T157-T157
Author(s):  
Anna Lord ◽  
Hillevi Englund ◽  
Fredrik Clausen ◽  
Lars Hillered ◽  
Frida Ekholm Pettersson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Transgenic Mice ◽  
Amyloid Β

scholarly journals Cerebral Microvascular Rather than Parenchymal Amyloid-β Protein Pathology Promotes Early Cognitive Impairment in Transgenic Mice

2013 ◽  
Vol 38 (3) ◽  
pp. 621-632 ◽  
Author(s):  
Wenjin Xu ◽  
Feng Xu ◽  
Maria E. Anderson ◽  
AnnMarie E. Kotarba ◽  
Judianne Davis ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein

scholarly journals Altered Amyloid-β Metabolism and Deposition in Genomic-based β-Secretase Transgenic Mice

2004 ◽  
Vol 279 (50) ◽  
pp. 52535-52542 ◽  
Author(s):  
Matthew J. Chiocco ◽  
Laura Shapiro Kulnane ◽  
Linda Younkin ◽  
Steve Younkin ◽  
Geneviève Evin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Transgenic Animals ◽  
Brain Regions ◽  
Primary Component ◽  
App Processing ◽  
Bace1 Expression ◽  
First Time

Amyloid-β (Aβ) the primary component of the senile plaques found in Alzheimer's disease (AD) is generated by the rate-limiting cleavage of amyloid precursor protein (APP) by β-secretase followed by γ-secretase cleavage. Identification of the primary β-secretase gene,BACE1, provides a unique opportunity to examine the role this unique aspartyl protease plays in altering Aβ metabolism and deposition that occurs in AD. The current experiments seek to examine how modulating β-secretase expression and activity alters APP processing and Aβ metabolismin vivo. Genomic-basedBACE1transgenic mice were generated that overexpress humanBACE1mRNA and protein. The highest expressingBACE1transgenic line was mated to transgenic mice containing human APP transgenes. Our biochemical and histochemical studies demonstrate that mice overexpressing bothBACE1andAPPshow specific alterations in APP processing and age-dependent Aβ deposition. We observed elevated levels of Aβ isoforms as well as significant increases of Aβ deposits in these double transgenic animals. In particular, the double transgenics exhibited a unique cortical deposition profile, which is consistent with a significant increase of BACE1 expression in the cortex relative to other brain regions. Elevated BACE1 expression coupled with increased deposition provides functional evidence for β-secretase as a primary effector in regional amyloid deposition in the AD brain. Our studies demonstrate, for the first time, that modulation ofBACE1activity may play a significant role in AD pathogenesisin vivo.

Relationship Between Chronic Noise Exposure, Cognitive Impairment, and Degenerative Dementia: Update on the Experimental and Epidemiological Evidence and Prospects for Further Research

2021 ◽  
Vol 79 (4) ◽  
pp. 1409-1427
Author(s):  
Lei Huang ◽  
Yang Zhang ◽  
Yongwei Wang ◽  
Yajia Lan
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Noise Exposure ◽  
Treatment Options ◽  
Experimental Studies ◽  
Amyloid Β ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Future Research ◽  
Degenerative Dementia

Degenerative dementia, of which Alzheimer’s disease is the most common form, is characterized by the gradual deterioration of cognitive function. The events that trigger and promote degenerative dementia are not clear, and treatment options are limited. Experimental and epidemiological studies have revealed chronic noise exposure (CNE) as a potential risk factor for cognitive impairment and degenerative dementia. Experimental studies have indicated that long-term exposure to noise might accelerate cognitive dysfunction, amyloid-β deposition, and tau hyperphosphorylation in different brain regions such as the hippocampus and cortex. Epidemiological studies are increasingly examining the possible association between external noise exposure and dementia. In this review, we sought to construct a comprehensive summary of the relationship between CNE, cognitive dysfunction, and degenerative dementia. We also present the limitations of existing evidence as a guide regarding important prospects for future research.

scholarly journals Amyloid biomarkers as predictors of conversion from mild cognitive impairment to Alzheimer’s dementia: a comparison of methods

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Arnd Sörensen ◽  
◽  
Ganna Blazhenets ◽  
Florian Schiller ◽  
Philipp Tobias Meyer ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cox Regression ◽  
Amyloid Β ◽  
Principal Component ◽  
Brain Regions ◽  
Alzheimer’S Dementia ◽  
Training Dataset ◽  
Alzheimer's Dementia ◽  
Cox Models

Abstract Background Amyloid-β (Aβ) PET is an established predictor of conversion from mild cognitive impairment (MCI) to Alzheimer’s dementia (AD). We compared three PET (including an approach based on voxel-wise Cox regression) and one cerebrospinal fluid (CSF) outcome measures in their predictive power. Methods Datasets were retrieved from the ADNI database. In a training dataset (N = 159), voxel-wise Cox regression and principal component analyses were used to identify conversion-related regions (Cox-VOI and AD conversion-related pattern (ADCRP), respectively). In a test dataset (N = 129), the predictive value of mean normalized 18F-florbetapir uptake (SUVR) in AD-typical brain regions (composite SUVR) or the Cox-VOI and the pattern expression score (PES) of ADCRP and CSF Aβ42/Aβ40 as predictors were compared by Cox models (corrected for age and sex). Results All four Aβ measures were significant predictors (p < 0.001). Prediction accuracies (Harrell’s c) showed step-wise significant increases from Cox-SUVR (c = 0.71; HR = 1.84 per Z-score increase), composite SUVR (c = 0.73; HR = 2.18), CSF Aβ42/Aβ40 (c = 0.75; HR = 3.89) to PES (c = 0.77; HR = 2.71). Conclusion The PES of ADCRP is the most predictive Aβ PET outcome measure, comparable to CSF Aβ42/Aβ40, with a slight but statistically significant advantage.

Sign in / Sign up

Export Citation Format

Share Document