Early Β-Amyloid Accumulation in the Brain Is Associated With Blood T and B Cell Alterations

2021 ◽  
Author(s):  
Christoph Gericke ◽  
Tunahan Kirabali ◽  
Roman Flury ◽  
Anna Mallone ◽  
Chiara Rickenbach ◽  
...  
Keyword(s):  
B Cell ◽  
Amyloid Accumulation ◽  
Β Amyloid ◽  
Cell Alterations ◽  
The Brain

scholarly journals Dysfunction of G Protein-Coupled Receptor Kinases in Alzheimer’'s Disease

2010 ◽  
Vol 10 ◽  
pp. 1667-1678 ◽  
Author(s):  
William Z. Suo ◽  
Longxuan Li
Keyword(s):  
G Protein ◽  
Basal Forebrain ◽  
Brain Inflammation ◽  
G Protein Coupled Receptor ◽  
Amyloid Accumulation ◽  
Cognitive Levels ◽  
Receptor Kinases ◽  
Β Amyloid ◽  
G Protein Coupled ◽  
The Brain

Although mutations and variations of several genes have been identified to be involved in Alzheimer's disease (AD), the efforts towards understanding the pathogenic mechanisms of the disease still have a long journey to go. One such effort is to identify the signal transduction deficits, for which previous studies have suggested that the central problems appear to be at the interface between G proteins and their coupled receptors. G protein-coupled receptor kinases (GRKs) are a small family of serine/threonine protein kinases primarily acting at the “receptor-G protein interface””. Recent studies have indicated the possible involvement of GRK, primarily GRK2 and GRK5, dysfunction in the pathogenesis of AD. It seems that mild, soluble, β-amyloid accumulation can lead to a reduced membrane (functional) and an elevated cytosolic GRK2/5. The increased cytosolic GRK2 appears to be colocalized with damaged mitochondria and neurofibrillary tangles. Moreover, the total levels of GRK2, not only in the brain, but also in peripheral blood samples, are increased in a manner inversely correlated with the patient's cognitive levels. The deficiency of GRK5, on the other hand, impairs presynaptic M2 autoreceptor desensitization, which leads to a reduced acetylcholine release, axonal/synaptic degenerative changes, and associated amnestic, mild cognitive impairment. It also promotes an evil cycle to further increase Beta-amyloid accumulation and exaggerates brain inflammation, possibly even the basal forebrain cholinergic degeneration. Therefore, continuous efforts in this direction are necessary before translating the knowledge to any therapeutic strategies.

scholarly journals Hypertension drives parenchymal β‐amyloid accumulation in the brain parenchyma

2014 ◽  
Vol 1 (2) ◽  
pp. 124-129 ◽  
Author(s):  
Celine Z. Bueche ◽  
Cheryl Hawkes ◽  
Cornelia Garz ◽  
Stefan Vielhaber ◽  
Johannes Attems ◽  
...  
Keyword(s):  
Brain Parenchyma ◽  
Amyloid Accumulation ◽  
Β Amyloid ◽  
The Brain

scholarly journals Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Toru Murakawa-Hirachi ◽  
Yoshito Mizoguchi ◽  
Masahiro Ohgidani ◽  
Yoshinori Haraguchi ◽  
Akira Monji
Keyword(s):  
Neuronal Death ◽  
Phagocytic Activity ◽  
Microglial Cell ◽  
Cell Function ◽  
Microglial Cells ◽  
Phagocytosis Assay ◽  
Intracellular Ca ◽  
Β Amyloid ◽  
The Brain

AbstractThe pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation of microglial cells in animal models of AD. However, it remains to be tested whether memantine can directly affect microglial cell function. In this study, we examined whether pretreatment with memantine affects intracellular NO and Ca2+ mobilization using DAF-2 and Fura-2 imaging, respectively, and tested the effects of memantine on phagocytic activity by human β-Amyloid (1–42) phagocytosis assay in rodent microglial cells. Pretreatment with memantine did not affect production of NO or intracellular Ca2+ elevation induced by TNF in rodent microglial cells. Pretreatment with memantine also did not affect the mRNA expression of pro-inflammatory (TNF, IL-1β, IL-6 and CD45) or anti-inflammatory (IL-10, TGF-β and arginase) phenotypes in rodent microglial cells. In addition, pretreatment with memantine did not affect the amount of human β-Amyloid (1–42) phagocytosed by rodent microglial cells. Moreover, we observed that pretreatment with memantine did not affect 11 major proteins, which mainly function in the phagocytosis and degradation of β-Amyloid (1–42), including TREM2, DAP12 and neprilysin in rodent microglial cells. To the best of our knowledge, this is the first report to suggest that memantine does not directly modulate intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells. Considering the neuroinflammation hypothesis of AD, the results might be important to understand the effect of memantine in the brain.

Novel quinoxaline derivatives for in vivo imaging of β-amyloid plaques in the brain

2011 ◽  
Vol 21 (14) ◽  
pp. 4193-4196 ◽  
Author(s):  
Mengchao Cui ◽  
Masahiro Ono ◽  
Hiroyuki Kimura ◽  
Boli Liu ◽  
Hideo Saji
Keyword(s):  
In Vivo Imaging ◽  
Amyloid Plaques ◽  
Quinoxaline Derivatives ◽  
Β Amyloid ◽  
The Brain

scholarly journals Concurrent Treatment with Taxifolin and Cilostazol on the Lowering of β-Amyloid Accumulation and Neurotoxicity via the Suppression of P-JAK2/P-STAT3/NF-κB/BACE1 Signaling Pathways

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168286 ◽  
Author(s):  
So Youn Park ◽  
Hae Young Kim ◽  
Hee Jeong Park ◽  
Hwa Kyoung Shin ◽  
Ki Whan Hong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Concurrent Treatment ◽  
Amyloid Accumulation ◽  
Β Amyloid

Visual-discrimination learning ability and β-amyloid accumulation in the dog

1998 ◽  
Vol 19 (5) ◽  
pp. 415-425 ◽  
Author(s):  
E. Head ◽  
H. Callahan ◽  
B.A. Muggenburg ◽  
C.W. Cotman ◽  
N.W. Milgram
Keyword(s):  
Discrimination Learning ◽  
Visual Discrimination ◽  
Learning Ability ◽  
Visual Discrimination Learning ◽  
Amyloid Accumulation ◽  
Β Amyloid

scholarly journals Parkin reverses intracellular β-amyloid accumulation and its negative effects on proteasome function

2009 ◽  
Vol 88 (1) ◽  
pp. 167-178 ◽  
Author(s):  
Kenneth M. Rosen ◽  
Charbel E.-H. Moussa ◽  
Han-Kyu Lee ◽  
Pravir Kumar ◽  
Tohru Kitada ◽  
...  
Keyword(s):  
Negative Effects ◽  
Amyloid Accumulation ◽  
Β Amyloid

scholarly journals Pre-therapeutic Microglia Activation and Sex Determine Therapy Effects of Chronic Immunomodulation

2021 ◽  
Author(s):  
Gloria Biechele ◽  
Tanja Blume ◽  
Maximilian Deussing ◽  
Benedikt Zott ◽  
Yuan Shi ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Learning Performance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Activated Microglia ◽  
Ppar Γ ◽  
Amyloid Accumulation ◽  
Β Amyloid

Modulation of the innate immune system is emerging as a promising therapeutic strategy against Alzheimer's disease (AD). However, determinants of a beneficial therapeutic effect are ill-understood. Thus, we investigated the potential of 18 kDa translocator protein positron-emission-tomography (TSPO-PET) for assessment of microglial activation in mouse brain before and during chronic immunomodulation. Serial TSPO-PET was performed during five months of chronic microglia modulation by stimulation of peroxisome proliferator-activated receptor (PPAR)-γ with pioglitazone in two different mouse models of AD (PS2APP, AppNL-G-F). Using mixed statistical models on longitudinal TSPO-PET data, we tested for effects of therapy and sex on treatment response. We tested correlations of baseline with longitudinal measures of TSPO-PET, and correlations between PET results with spatial learning performance and β-amyloid accumulation of individual mice. Immunohistochemistry was used to determine the molecular source of the TSPO-PET signal. Pioglitazone-treated female PS2APP and AppNL-G-F mice showed attenuation of the longitudinal increases in TSPO-PET signal when compared to vehicle controls, whereas treated male AppNL-G-F mice showed the opposite effect. Baseline TSPO-PET strongly predicted changes in microglial activation in treated mice (R=-0.874, p<0.0001) but not in vehicle controls (R=-0.356, p=0.081). Reduced TSPO-PET signal upon treatment was associated with better spatial learning and higher fibrillar β-amyloid accumulation. Immunohistochemistry confirmed activated microglia to be the source of the TSPO-PET signal (R=0.952, p<0.0001). TSPO-PET represents a sensitive biomarker for monitoring of immunomodulation and closely reflects activated microglia. Pre-therapeutic assessment of baseline microglial activation and sex are strong predictors of individual immunomodulation effects and could serve for responder stratification.

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