Astrocytes primarily maintain physiological brain homeostasis. However, under various pathological conditions, they can undergo morphological, transcriptomic, and functional transformations, collectively referred to as reactive astrogliosis. Recent studies have accumulated lines of evidence that reactive astrogliosis plays a crucial role in the pathology of Alzheimer's disease (AD). In particular, monoamine oxidase B, a mitochondrial enzyme mainly expressed in astrocytes, significantly contributes to neuronal dysfunction and neurodegeneration in AD brains. Moreover, it has been reported that reactive astrogliosis precedes other pathological hallmarks such as amyloid-beta plaque deposition and tau tangle formation in AD. Due to the early onset and profound impact of reactive astrocytes on pathology, there have been extensive efforts in the past decade to visualize these cells in the brains of AD patients using positron emission tomography (PET) imaging. In this review, we summarize the recent studies regarding the essential pathological importance of reactive astrocytes in AD and their application as a target for PET imaging.
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http://dx.doi.org/10.1007/s13139-023-00837-y | DOI Listing |
Alzheimers Dement
December 2024
Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.
Background: Alzheimer's disease (AD) is associated with synaptic and memory dysfunction. A pathological hallmark of the disease is reactive astrogliosis, with reactive astrocytes surrounding amyloid plaques in the brain. Astrocytes have also been shown to be actively involved in disease progression, nevertheless, mechanistic information about their role in synaptic transmission during AD pathology is lacking.
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December 2024
UK Dementia Research Institute @ University College London, London, United Kingdom.
Background: Astrocytes are a numerous and diverse glial subtype specialised to carry out distinct roles involving maintaining homeostasis and effective functioning of the nervous system. To do so effectively, they respond to and secrete various proteins. In addition, astrocytes have been linked to Alzheimer's disease (AD), where they are believed to become reactive and contribute to neuroinflammation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Kentucky, Lexington, KY, USA.
Background: Compared with the E3 allele of Apolipoprotein E (APOE), E4 increases late-onset Alzheimer's Disease (AD) risk up to 15-fold, while the E2 allele substantially decreases risk. In the CNS, ApoE is predominantly synthesized by astrocytes and microglia, making these two cell types promising targets for ApoE-directed therapeutic approaches. Our lab has generated an inducible "switch" mouse model (APOE4s2) in which we can conditionally replace E4 with the protective E2 in a cell-specific manner.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: Down syndrome (DS) is characterized by the overexpression of the amyloid precursor protein gene (APP) and pro-inflammatory genes, leading to progressive beta-amyloid (Aβ) accumulation. This accumulation in DS may exacerbate neuroinflammation, contributing to the pathogenesis of Alzheimer's Disease (AD). Experimental models suggest that aquaporin 4 (AQP4), an astrocytic water channel implicated in Aβ clearance, is mislocalized with increased Aβ burden.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pittsburgh, Pittsburgh, PA, USA.
Background: Vascular cognitive impairment/dementia (VD) is the second most prevalent cause of dementia following Alzheimer's disease (AD). VD is characterized by the progression of white matter hyperintensity burden (WMH) and associated neurodegeneration. GFAP, a biomarker for reactive astrogliosis, is associated with Aβ pathology and mediates tau-pathology in preclinical AD.
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