Intramuscular delivery of a single chain antibody gene reduces brain Aβ burden in a mouse model of Alzheimer's disease

Wang, Yan‐Jiang; Pollard, Anthony; Zhong, Jin‐Hua; Dong, Xiaoyan; Wu, Xiaobing; Zhou, Huadong; Zhou, Xin‐Fu

doi:10.1016/j.neurobiolaging.2007.06.013

Cited by 51 publications

(49 citation statements)

References 42 publications

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“…67 They also include ScFv fragments that effect peripheral non-inflammatory Ab clearance using novel recombinant adenoassociated virus (AAV) vectors to carry and express the ScFv following intramuscular administration (gene-activated therapy). 68 Intramuscular administration was as effective as intracranial delivery of the AAV vector in reducing brain Ab burden in a murine AD model, suggesting systemic clearance is potentially an effective therapeutic strategy. 68 0 500 1000 1500 2000 2500…”

Section: Synthetic Ab-binding Agents As Diagnostic Toolsmentioning

confidence: 95%

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Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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Currently, the 'amyloid hypothesis' is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-b (Ab) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Ab is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Ab leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Ab are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Ab clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Ab ELISAs are discussed, as are the more promising results of Ab imaging by positron emission tomography. Current knowledge of Ab-binding proteins and Ab-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood-brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Ab remains an attractive therapeutic strategy, and improved understanding of Ab clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.

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Section: Synthetic Ab-binding Agents As Diagnostic Toolsmentioning

confidence: 95%

“…68 Intramuscular administration was as effective as intracranial delivery of the AAV vector in reducing brain Ab burden in a murine AD model, suggesting systemic clearance is potentially an effective therapeutic strategy. 68 0 500 1000 1500 2000 2500…”

Section: Synthetic Ab-binding Agents As Diagnostic Toolsmentioning

confidence: 95%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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“…The staining for brain total Ab, microgliosis, astrogliosis and microhaemorrhage was processed as described previously (Wang et al 2009). Briefly, three series of six equally spaced tissue sections (*200 lm apart) spanning the hippocampus were randomly selected and stained using free-floating immunohistochemistry for total Ab (Biotinconjugated mouse anti-Ab antibody 6E10, Serotec, USA; 1:1000 dilution), activated microglia (rat monoclonal anti-CD45, Chemicon, USA; 1:2000 dilution) and astrocyte (rabbit polyclonal anti-glial fibrillary acidic protein, Dako, Denmark; 1:1000 dilution), respectively.…”

Section: Ad-type Pathology and Quantitative Image Analysismentioning

confidence: 99%

“…Quantification of Ab Peptide Levels in the Mouse Brain and Plasma by ELISA ELISA analysis of the brain Ab was processed as described previously (Wang et al 2009). Briefly, frozen brain was homogenized and sonicated in water containing 2% sodium dodecyl sulphate (SDS) and protease inhibitors (Boehringer Mannheim, Germany).…”

Section: Ad-type Pathology and Quantitative Image Analysismentioning

confidence: 99%

Consumption of Grape Seed Extract Prevents Amyloid-β Deposition and Attenuates Inflammation in Brain of an Alzheimer’s Disease Mouse

et al. 2009

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Polyphenols extracted from grape seeds are able to inhibit amyloid-beta (Abeta) aggregation, reduce Abeta production and protect against Abeta neurotoxicity in vitro. We aimed to investigate the therapeutic effects of a polyphenol-rich grape seed extract (GSE) in Alzheimer's disease (AD) mice. APP(Swe)/PS1dE9 transgenic mice were fed with normal AIN-93G diet (control diet), AIN-93G diet with 0.07% curcumin or diet with 2% GSE beginning at 3 months of age for 9 months. Total phenolic content of GSE was 592.5 mg/g dry weight, including gallic acid (49 mg/g), catechin (41 mg/g), epicatechin (66 mg/g) and proanthocyanidins (436.6 mg catechin equivalents/g). Long-term feeding of GSE diet was well tolerated without fatality, behavioural abnormality, changes in food consumption, body weight or liver function. The Abeta levels in the brain and serum of the mice fed with GSE were reduced by 33% and 44%, respectively, compared with the Alzheimer's mice fed with the control diet. Amyloid plaques and microgliosis in the brain of Alzheimer's mice fed with GSE were also reduced by 49% and 70%, respectively. Curcumin also significantly reduced brain Abeta burden and microglia activation. Conclusively, polyphenol-rich GSE prevents the Abeta deposition and attenuates the inflammation in the brain of a transgenic mouse model, and this thus is promising in delaying development of AD.

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“…special importance in treatment of AD. Both clinical and experimental findings demonstrated that anti-Aβ antibodies could reduce and/or reverse AD pathology, while the mechanism is still not clear (Liu et al, 2004;Fukuchi et al, 2006;Zameer et al, 2006;Melnikova, 2007;Wang et al, 2007;Solórzano-Vargas et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

The toxicity of β-amyloid is attenuated by interaction with its specific human scFv E3 in vitro

Shen

Wang

et al. 2008

Life Sciences

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Intramuscular delivery of a single chain antibody gene reduces brain Aβ burden in a mouse model of Alzheimer's disease

Cited by 51 publications

References 42 publications

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Consumption of Grape Seed Extract Prevents Amyloid-β Deposition and Attenuates Inflammation in Brain of an Alzheimer’s Disease Mouse

The toxicity of β-amyloid is attenuated by interaction with its specific human scFv E3 in vitro

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