Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease

Itagaki, S.; McGeer, Patrick L.; Akiyama, Haruhiko; Zhu, Shi G.; Selkoe, Dennis J.

doi:10.1016/0165-5728(89)90115-x

Cited by 864 publications

(527 citation statements)

References 19 publications

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“…These observations suggest that SPs sequester the remnants of degenerating and/or dying neurons and their processes during their formation. Microglial cells have been detected within SPs, and astrocytosis occurs around SPs (15,67,68), but relatively low levels of glial-derived mRNAs are seen in SPs, which may also reflect a lower abundance of RNAs in glial cells (17). …”

Section: Single Cell Analysis In Ad: Senile Plaquesmentioning

confidence: 99%

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

et al. 2004

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Technical and experimental advances in microaspiration techniques, RNA amplification, quantitative real-time polymerase chain reaction (qPCR), and cDNA microarray analysis have led to an increase in the number of studies of single-cell gene expression. In particular, the central nervous system (CNS) is an ideal structure to apply single-cell gene expression paradigms. Unlike an organ that is composed of one principal cell type, the brain contains a constellation of neuronal and noneuronal populations of cells. A goal is to sample gene expression from similar cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and noneuronal cells. The unprecedented resolution afforded by singlecell RNA analysis in combination with cDNA microarrays and qPCR-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease states. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models as well as postmortem human brain tissues. This focused review illustrates the potential power of single-cell gene expression studies within the CNS in relation to neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia, respectively. KEY WORDS:Alzheimer's disease; cDNA microarray; cholinergic basal forebrain; dopamine receptors; expression profiling; protein phosphatases; RNA amplification; schizophrenia; single-cell microaspiration. Abbreviations (note the use of the NCBI-Unigene annotation): 3Rtau, three-repeat tau; 4Rtau, four-repeat tau; ACT, alpha-1-antichymotrypsin; ACTB, beta-actin; AGER, advanced glycosylation end product-specific receptor; APOE, apolipoprotein E; APP, amyloid-beta precursor protein; arc, activity regulated cytoskeletal-associated protein; BAX,

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Section: Single Cell Analysis In Ad: Senile Plaquesmentioning

confidence: 99%

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

et al. 2004

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“…In the AD brain, activated microglia are found in the direct vicinity of Aβ plaques (D'Andrea et al, 2004;Itagaki et al, 1989). Initially, they take on a neuroprotective role by releasing amyloid-degrading enzymes for the clearance of amyloid fibrils in the early stages of the disease.…”

Section: Supplementary Introductionmentioning

confidence: 99%

Imaging microglial activation and glucose consumption in a mouse model of Alzheimer's disease

Rapic

Backes

Viel

et al. 2013

Neurobiology of Aging

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Abstract. In Alzheimer´s disease (AD), persistent microglial activation as sign of chronic neuroinflammation contributes to disease progression. Our study aimed to in vivo visualize and quantify microglial activation in 13-to 15-month-old AD mice using [ 11 C]-(R)-PK11195 and positron emission tomography (PET). We attempted to modulate neuroinflammation by subjecting the animals to an anti-inflammatory treatment with pioglitazone (5-weeks' treatment, 5-week wash-out period).[ 11 C]-(R)-PK11195 distribution volume values in AD mice were significantly higher compared with control mice after the wash-out period at 15 months, which was supported by immunohistochemistry data. However, [ 11 C]-(R)-PK11195 µPET could not demonstrate genotype-or treatment-dependent differences in the 13-to 14 month-old animals, suggesting that microglial activation in AD mice at this age and disease stage is too mild to be detected by this imaging method.Introduction. In AD, activated microglia are found in the direct vicinity of amyloid β (Aβ) plaques.

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“…The close association of micro. glial cells with senile plaques has led to the hypothesis that microglia are the producers and processors offlAP [25,26] although it has also been suggested that amyloid deposition precedes microglial involvement [27][28][29]. Astrocytes, which appear in high numbers and in close proximity to senile plaques [30,31] and have been shown to have elevated levels of APP expression in lesioned brains [32] could also play a role in flAP deposition.…”

Section: Introductionmentioning

confidence: 99%

Differential APP gene expression in rat cerebral cortex, meninges, and primary astroglial, microglial and neuronal cultures

et al. 1991

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Differential amyloid precursor protein (APP) gene expression wag investigated ~r. primary cultures of astrocytes, neurons and microglia from neonatal rat cerebral cortex as well as in meninges, and young and adult cerebral cortex tissues in order to define the possible contribution of individual CNS cell types in flAP deposition. Meninges and neurons contained higher levels of total APP mRNA than glial cells and APP6gs mRNA was abundant in neurons while glial ceils and meninges contained higher levels of KPI-containing mRNAs. These results demonstrate cell-specific transcriptional and post-transcriptional regulation of APP gene expression in CNS cell types. In addition, the steady-state level of APPs ha each cell type did not reflect mRNA levels indicating translational or post-translational regulation.

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Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease

Cited by 864 publications

References 19 publications

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

Imaging microglial activation and glucose consumption in a mouse model of Alzheimer's disease

Differential APP gene expression in rat cerebral cortex, meninges, and primary astroglial, microglial and neuronal cultures

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