Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease

Nagele, Robert G.; Węgiel, Jerzy; Venkataraman, Venkat; Imaki, Humi; Wang, Kuo-Chiang; Wegiel, J.

doi:10.1016/j.neurobiolaging.2004.01.007

Cited by 449 publications

(320 citation statements)

References 56 publications

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“…1); this astrogliosis was observed in both human tissues and in the brains isolated from AD animal models. [147][148][149][150] …”

Section: Astroglia In Alzheimer's Diseasementioning

confidence: 99%

“…Generalized astrogliosis, manifested by cellular hypertrophy and by an increase in expression of GFAP and astroglial S100B protein, was routinely observed in postmortem tissues from AD patients. 148,[151][152][153][154][155][156] More detailed analysis of astrogliosis in the brains obtained from old patients (with and without confirmed AD) have demonstrated a correlation between the degree of astrogliosis and cognitive decline; however, the same analysis failed to reveal a direct correlation between astrogliotic changes and senile plaques. 157 The morphological data showed reactive astrocytes associated with some, but not with all A␤ plaques; astrogliotic fields were also found in areas without A␤ depositions in both AD and non-AD brains.…”

Section: Morphology and Numbersmentioning

confidence: 99%

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Astrocytes in Alzheimer's Disease

et al. 2010

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Summary:The circuitry of the human brain is formed by neuronal networks embedded into astroglial syncytia. The astrocytes perform numerous functions, providing for the overall brain homeostasis, assisting in neurogenesis, determining the micro-architecture of the grey matter, and defending the brain through evolutionary conserved astrogliosis programs.Astroglial cells are engaged in neurological diseases by determining the progression and outcome of neuropathological process. Astrocytes are specifically involved in various neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and various forms of dementia. Recent evidence suggest that early stages of neurodegenerative processes are associated with atrophy of astroglia, which causes disruptions in synaptic connectivity, disbalance in neurotransmitter homeostasis, and neuronal death through increased excitotoxicity. At the later stages, astrocytes become activated and contribute to the neuroinflammatory component of neurodegeneration.

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“…1); this astrogliosis was observed in both human tissues and in the brains isolated from AD animal models. [147][148][149][150] …”

Section: Astroglia In Alzheimer's Diseasementioning

confidence: 99%

Section: Morphology and Numbersmentioning

confidence: 99%

Astrocytes in Alzheimer's Disease

et al. 2010

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“…53 In the AD human tissue the main astroglial reaction found hitherto is represented by prominent astrogliosis, mostly observed in the cells surrounding amyloid plaques. 54 Importantly, activated astrocytes are capable of accumulating large amounts of Ab; 55 the later being taken up by astrocytes in association with neuronal debris. In addition, reactive astrocytes seem to accumulate large amounts of neuronal subtype of nicotinic cholinoreceptor (a7nAChRs), which is known to have an exceptionally high affinity to b-amyloid.…”

Section: Astroglia and Alzheimer's Diseasementioning

confidence: 99%

“…Astroglial b-amyloid deposits are clearly associated with plaques, as astrocytes positioned away from the plaques show no b-amyloid burden. 54,55 Processes of activated astrocytes were also reported to participate in plaques formation. 54,55 At the very same time astroglial changes during AD progression remain virtually unexplored.…”

Section: Astroglia and Alzheimer's Diseasementioning

confidence: 99%

Astroglia in dementia and Alzheimer's disease

et al. 2008

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Astrocytes, the most numerous cells in the brain, weave the canvas of the grey matter and act as the main element of the homoeostatic system of the brain. They shape the microarchitecture of the brain, form neuronal-glial-vascular units, regulate the blood-brain barrier, control microenvirionment of the central nervous system and defend nervous system against multitude of insults. Here, we overview the pathological potential of astroglia in various forms of dementias, and hypothesise that both atrophy of astroglia and reactive hypertrophic astrogliosis may develop in parallel during neurodegenerative processes resulting in dementia. We also show that in the transgenic model of Alzheimer's disease, reactive hypertrophic astrocytes surround the neuritic plaques, whereas throughout the brain parenchyma astroglial cells undergo atrophy. Astroglial atrophy may account for early changes in synaptic plasticity and cognitive impairments, which develop before gross neurodegenerative alterations.

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“…Neuronal excitotoxicity leading to neuronal death [34,35] Hyperphosphorylated tau Formation of neurofibrillary tangles [36,37] Inflammation Exacerbation of tau pathology [38] , induction of Aβ release from neurons [39] , attenuation of long-term potentiation [40] , retraction of synapses [41] Metal ion dyshomeostasis Promotion of Aβ aggregation [42,43] Mutations in genes for presenillin-1 and -2, and Increased Aβ levels, linked to Aβ accumulation [44][45][46] amyloid precursor protein; ApoE 4 allele genotype Neurosci Bull February 1, 2013, 29(1): 111-120 114 thologies leads to increased Aβ production [67] . This finding may well explain the sporadic AD which does not involve mutations of genes implicated in Aβ generation.…”

Section: Glutamate Increasesmentioning

confidence: 99%

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

et al. 2012

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There is no effective drug to treat Alzheimer's disease (AD), a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta (Aβ) may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors (NTFs). Evidence from clinical trials has shown that both Aβ clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aβ clearance and administration of NTFs may be an effective therapeutic strategy.Keywords: Alzheimer's disease; amyloid-beta; neurotrophic factors; treatment IntroductionAlzheimer's disease (AD) is an age-related, progressive and irreversible neurodegenerative disease that causes serious cognitive dysfunction. Its pathological hallmarks are extracellular deposits of amyloid-beta (Aβ) and intracellular neurofibrillary tangles, together with drastic synaptic and neuronal reduction or loss [1] . It has been estimated that AD affects 30 million people around the world [2] , and the past two decades have witnessed an explosion in research into the underlying mechanisms as well as potential therapeutic strategies. Although it was first described by German psychiatrist Alois Alzheimer in 1906, there is still no cure for AD, partly because the cellular and molecular mechanisms underlying it are far from clear. The Food and Drug Administration in the United Stateshas approved a limited range of drugs to treat AD, including acetylcholinesterase inhibitors (AChEIs) and N-methyl-Daspartate receptor (NMDAR) antagonists [3] , although their effects are merely symptomatic and memory-improvement occurs within a limited period. Donepezil, galantamine, rivastigmine and tacrine are AChEIs that prevent the breakdown of acetylcholine released from presynaptic terminals, increasing the residence time of the neurotransmitter within the synapse and thereby prolonging the duration of its interaction with postsynaptic receptors [4] . Memantine, an NMDAR antagonist, has been approved for the treatment of moderate and severe AD; it works by preventing the excitatory neurotoxicity induced by excessive glutamate [5] .Currently, no available pharmacological agents cure or reverse the progression of this devastating neurological disorder. It is therefore urgent to improve our understanding of its pathogenesis, and then develop an effective treatment strategy. This review aimed to provide insights Neurosci Bull February 1, 2013, 29(1): 111-120 112 into the design of potentially effective pharmaceutical treatments for AD by targeting two seemingly separate but tightly connected components, Aβ and neurotrophic factors (NTFs). Aβ as a Promising Target for AD TreatmentAβ is a peptide of 36-43 amino-acids produced from amyloid precursor protein (APP) through aberrant cleavage by...

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Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease

Cited by 449 publications

References 56 publications

Astrocytes in Alzheimer's Disease

Astrocytes in Alzheimer's Disease

Astroglia in dementia and Alzheimer's disease

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

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