Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse

Gordon, Marcia N.; Holcomb, Leigh A.; Jantzen, Paul T.; DiCarlo, Giovanni; Wilcock, Donna M.; Boyett, Kristal W.; Connor, Karen E.; Melachrino, Jason; O’Callaghan, James P.; Morgan, Dave

doi:10.1006/exnr.2001.7754

Cited by 223 publications

(193 citation statements)

References 40 publications

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“…The transgenic mouse models of AD show that amyloid deposition progressively develops throughout the mouse brain [12]. In the mouse models that express mutated human app, ps-1, or ps-2 genes, substantial amyloid deposition is not apparent prior to 9 months of age.…”

Section: Experimental Models Of Admentioning

confidence: 99%

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Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

Little

Hammond

MacIntyre

et al. 2004

Neurobiology of Aging

202

197

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Amyloid deposits resembling plaques found in Alzheimer's disease (AD) brains were formed in the brains of non-transgenic BALB/c mice following intranasal infection with Chlamydia pneumoniae. The mice were infected at 3 months of age with C. pneumoniae isolated from an AD brain. Infection was confirmed by light and electron microscopy in olfactory tissues of the mice. C. pneumoniae was still evident in these tissues 3 months after the initial infection indicating that a persistent infection had been established. Amyloid beta (A␤) 1-42 immunoreactive deposits were identified in the brains of infected BALB/c mice up to 3 months post-infection with the density, size, and number of deposits increasing as the infection progressed. A subset of deposits exhibited thioflavin-s labeling. Intracellular A␤1-42 labeling was observed in neuronal cells. Experimental induction of amyloid deposition in brains of non-transgenic BALB/c mice following infection with C. pneumoniae may be a useful model for furthering our understanding of mechanisms, linked to infection, involved in the initiation of the pathogenesis of sporadic AD.

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Section: Experimental Models Of Admentioning

confidence: 99%

“…Previous models of Alzheimer's disease have utilized transgenic mice over-expressing the well-characterized mutants of presenilin and gene products of beta amyloid precursor protein [12,36]. The over-expression of amyloid results in the development of amyloid plaques in the brain, paralleling the pathology observed in familial AD [13].…”

Section: Introductionmentioning

confidence: 99%

Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

Little

Hammond

MacIntyre

et al. 2004

Neurobiology of Aging

202

197

View full text Add to dashboard Cite

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“…Through mutations, these mice 3 overexpress both the Aβ precursor protein (APP) and presenilin 1 (PS1) gene, causing rapid development of Aβ plaques clustered by activated microglia together with the exhibition of behavioral deficits (Garcia-Alloza et al, 2006;Gordon et al, 2002;Yan et al, 2009). …”

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 present study used PSAPP doubly transgenic mice generated by mating the Tg2576 mouse line carrying the 'Swedish' APP mutation (APP K670NM671L ) (Hsiao et al, 1996) with a mutant presenilin-1 mouse line (PS-1 M146L6.2 ) (Duff et al, 1996). The combination of these two mutations results in an increased production of amyloid β peptide with initial deposition of plaques detectable as early as 3-4 months of age (Emilien et al, 2000;Holcomb et al, 1998;Holcomb et al, 1999;McGowan et al, 1999;Gordon et al, 2002). PSAPP mice provide a rapid means of screening agents that affect amyloid β.…”

Section: Introductionmentioning

confidence: 99%

Centella asiatica extract selectively decreases amyloid β levels in hippocampus of Alzheimer's disease animal model

Dhanasekaran

Holcomb

Hitt

et al. 2008

Phytotherapy Research

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165

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PSAPP mice expressing the 'Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid β β β β β plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid β β β β β 1-40 and 1-42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid β β β β β pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease.

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Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse

Cited by 223 publications

References 40 publications

Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

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

Centella asiatica extract selectively decreases amyloid β levels in hippocampus of Alzheimer's disease animal model

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