Progressive Neuronal Injury Associated with Amyloid Plaque Formation in Alzheimer Disease

Sheng, Jin; Zhou, Xue; Mrak, Robert E.; Griffin, W. Sue T.

doi:10.1097/00005072-199807000-00008

Cited by 76 publications

(38 citation statements)

References 15 publications

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“…24 Some investigators contend that the stages of plaque development and resultant neuronal damage begin with the formation of the diffuse plaque, which then advances to the neuritic variety and eventually concludes with the burnt-out type. 24,39 There is, however, no direct evidence that an evolution of plaque formation occurs.…”

Section: What Are Plaques?mentioning

confidence: 99%

Neuropathology for the Neuroradiologist: Plaques and Tangles

Wippold¹,

Cairns²,

Vo³

et al. 2007

AJNR Am J Neuroradiol

140

164

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Section: What Are Plaques?mentioning

confidence: 99%

Neuropathology for the Neuroradiologist: Plaques and Tangles

Wippold¹,

Cairns²,

Vo³

et al. 2007

AJNR Am J Neuroradiol

140

164

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“…The right hippocampus and adjacent mesial temporal cortex at the level of lateral geniculate nucleus were processed as previously described (Sheng et al, 1998b) for Tdt-mediated dUTP nick end labeling (TUNEL) and immunohistochemical studies.…”

Section: Tissue Processingmentioning

confidence: 99%

“…TUNEL was performed as previously described (Sheng et al, 1998b) using an in situ Cell Death Detection Kit-POD (Boehringer-Mannheim Biochemica), and either directly examined using fluorescence microscopy or indirectly assayed by incubating with antifluorescein-POD for 30 min and visualizing with metal-enhanced diaminobenzidine substrate by light microscopical analysis.…”

Section: Tunel Labelingmentioning

confidence: 99%

“…Increasing data suggest that such neurons, undergoing cell death either by a form of apoptosis or necrosis, manifest significant DNA fragmentation (Anderson et al, 1996;Sheng et al, 1998b;Smale et al, 1995;Velez-Pardo et al, 2001). The number of neurons having fragmented DNA (fDNA) correlates with the formation of neurofibrillary tangles in those neurons (Sheng et al, 1998b). Moreover, the number of DNA-damaged neurons found within or very near plaques increases as plaques mature from simple diffuse Aβ deposits to the more complex neuritic plaques, which are diagnostic of AD.…”

Section: Introductionmentioning

confidence: 99%

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Microglial activation by uptake of fDNA via a scavenger receptor

Liu

et al. 2004

Journal of Neuroimmunology

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The fate of the fragmented DNA (fDNA) observed in neuronal nuclei in Alzheimer brain is unknown. However, its fate is suggested as fDNA is found in the cytoplasm of adjacent activated microglia. After a brief incubation with fDNA, approximately 70% of microglia had fDNA in their cytoplasm, were activated, and overexpressed interleukin-1β. Microglial activation enhanced uptake whereas blocking scavenger receptors suppressed this uptake. These results suggest that the brain rids itself of fDNA from dying neurons through microglial uptake, activation, and overexpression of IL-1. Such overexpression of IL-1 in Alzheimer brain has been linked to Alzheimer pathogenesis.

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“…In addition to neurofibrillary tangles (NFT) and beta amyloid protein (BAP) deposits, abundant apoptotic neuronal and glial cells are another pathological hallmark of AD [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Abnormal phosphorylation of the tau protein that leads to NFT formation, BAP deposits, high concentration of amyloid precursor protein (APP), caspase-3, the presenilin 1 and 2 gene and nitric oxide are considered to be important triggers of neuronal and glial apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Association of phosphorylation site of tau protein with neuronal apoptosis in Alzheimer's disease

Kobayashi

Nakano

Hayashi

et al. 2003

Journal of the Neurological Sciences

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In addition to neuritic changes and amyloid deposits, neuronal and glial cell apoptosis is an important pathological feature of Alzheimer's disease (AD). Several factors have been postulated as causes or triggers of cellular apoptotic change. This study focused on a quantifiable relationship between phosphorylation sites of tau protein in the neurofibrillary tangles (NFT) and neuronal apoptosis. Five monoclonal anti-tau antibodies (AT180, AT8, HT7, Tau2 and Tau5) for NFT labeling and TdT-mediated UTP nick-end labeling (TUNEL) for localizing apoptotic change were employed. TUNEL-stained neuronal nuclei showed significantly high density in the entorhinal cortex, cornu ammonis (CA) and the parietal cortex. In all regions, density of TUNEL-stained neuronal nuclei showed significantly direct correlation with that of AT8-, AT180-and Tau2-positive neurons. Correlation of TUNEL-stained neuronal nuclei with tau-positive neurons differed depending on the cerebral regions. Density of TUNEL-stained neuronal nuclei showed inverse correlation with that of both AT8-positive and Gallyas-stained NFT in the CA and showed significantly direct correlation with AT8-and HT7-positive neurons in the frontal cortex. Density of tau-positive and Gallyas-stained NFT was higher than that of TUNEL-stained nuclei. We conclude that phosphorylation sites of tau, 159-163 and 202-205, are probably associated with neuronal apoptosis and apoptotic change follows abnormal phosphorylation of tau.2 Introduction Apoptosis, a programmed cell death by intrinsic mechanism to regulate cell population, has been shown to occur extensively in brains from patients with Alzheimer's disease (AD). In addition to neurofibrillary tangles (NFT) and beta amyloid protein (BAP) deposits, abundant apoptotic neuronal and glial cells are another pathological hallmark of AD [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Abnormal phosphorylation of the tau protein that leads to NFT formation, BAP deposits, high concentration of amyloid precursor protein (APP), caspase-3, the presenilin 1 and 2 gene and nitric oxide are considered to be important triggers of neuronal and glial apoptosis . Since NFT are present in the neuronal cytoplasm, NFT and neuronal apoptosis have been considered to be intimately associated with each other. To the best of our knowledge, 13 studies, ten in vivo [1, 3, 5, 7, 8-10, 13, 16, 18] and three in vitro [15,18,22], have addressed the relationship between NFT formation and neuronal apoptosis. However, it is still unclear whether neuronal apoptosis is a result or cause of abnormal phosphorylation of tau.Tau immunohistochemistry has differentiated pretangle neurons, known as stage 0 tangles [26][27], from argyrophilic NFT, and phosphorylation sites of the amino acid sequence of tau molecules have been analyzed in AD brains [28][29]. The pretangle neurons are believed to occur in the early stage and may disappear in the late stage of AD with some of them remaining unchanged. A recent study has demonstrated that neurons with ...

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Progressive Neuronal Injury Associated with Amyloid Plaque Formation in Alzheimer Disease

Cited by 76 publications

References 15 publications

Neuropathology for the Neuroradiologist: Plaques and Tangles

Neuropathology for the Neuroradiologist: Plaques and Tangles

Microglial activation by uptake of fDNA via a scavenger receptor

Association of phosphorylation site of tau protein with neuronal apoptosis in Alzheimer's disease

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