An improved thioflavine S method for staining neurofibrillary tangles and senile plaques in Alzheimer's disease

Guntern, R.; Bouras, Constantin; Hof, Patrick R.; Vallet, Philippe

doi:10.1007/bf01923594

Cited by 125 publications

(76 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To determine whether the immunoreactive deposits observed in the unc-54/13-(1-42) strains display the tinctural properties of classic insoluble 3-amyloid, transgenic strains were fixed and stained with thioflavin S, a fluorescent amyloidspecific dye (37). Thioflavin S-reactive deposits were found in all strains containing the unc-54/13-(1-42) minigene construct, but not in control wild-type animals or strains containing either the unc-54/transthyretin or unc-54/transthyretin ala6O constructs.…”

Section: Resultsmentioning

confidence: 99%

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Link

1995

Proc. Natl. Acad. Sci. U.S.A.

618

511

View full text Add to dashboard Cite

Transgenic Caenorhabditis elegans nematodes have been engineered to express potentially amyloidic human proteins. These animals contain constructs in which the muscle-specific unc-54 promoter/enhancer of C. elegans drives the expression of the appropriate coding regions derived from human cDNA clones. Animals containing constructs expressing the 42-amino acid f3-amyloid peptide (derived from human amyloid precursor protein cDNA) produce muscle-specific deposits immunoreactive with anti-,3-amyloid polyclonal and monoclonal antibodies. A subset of these deposits also bind the amyloid-specific dye thioflavin S, indicating that these deposits have the tinctural characteristics of classic amyloid. Coexpression of f3-peptide and transthyretin, a protein implicated in preventing the formation of insoluble 13-amyloid, leads to a dramatic reduction in the number of dye-reactive deposits. These results suggest that this invertebrate model may be useful for in vivo investigation of factors that modulate amyloid formation.

show abstract

Section: Resultsmentioning

confidence: 99%

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Link

1995

Proc. Natl. Acad. Sci. U.S.A.

618

511

View full text Add to dashboard Cite

show abstract

“…Brain autopsy cases of AD, DLBD, LBV, and controls were selected for this study based on availability. The diagnosis of AD was based on densities of neuritic plaques, detected using a modified thioflavin S stain, 23 meeting the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for "definite AD". 24 Seventeen of the 19 AD cases selected in this manner had a Braak neurofibrillary tangle stage 25 of at least V, and the remaining two cases had a Braak stage of IV.…”

Section: Autopsy Brain Samples and Neuropathologic Examinationmentioning

confidence: 99%

Abnormal Neurites Containing C-Terminally Truncated α-Synuclein Are Present in Alzheimer's Disease without Conventional Lewy Body Pathology

Lewis

Jou

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

The pathological hallmark of Parkinson's disease and diffuse Lewy body disease (DLBD) is the aggregation of ␣-synuclein (␣-syn) in the form of Lewy bodies and Lewy neurites. Patients with both Alzheimer's disease (AD) and cortical Lewy pathology represent the Lewy body variant of AD (LBV) and constitute 25% of AD cases. C-terminally truncated forms of ␣-syn enhance the aggregation of ␣-syn in vitro. To investigate the presence of C-terminally truncated ␣-syn in DLBD, AD, and LBV, we generated and validated polyclonal antibodies to truncated ␣-syn ending at residues 110 (␣-syn110) and 119 (␣-syn119), two products of 20S proteosome-mediated endoproteolytic cleavage. Double immunofluorescence staining of the cingulate cortex showed that ␣-syn110 and ␣-syn140 (full-length) aggregates were not colocalized in LBV. All aggregates containing ␣-syn140 also contained ␣-syn119; however, some aggregates contained ␣-syn119 without ␣-syn140, suggesting that ␣-syn119 may stimulate aggregate formation. Immunohistochemistry and image analysis of tissue microarrays of the cingulate cortex from patients with DLBD (n ‫؍‬ 27) , LBV (n ‫؍‬ 27) , and AD (n ‫؍‬ 19) and age-matched controls (n ‫؍‬ 15) revealed that AD is also characterized by frequent abnormal neurites containing ␣-syn119. Notably, these neurites did not contain ␣-syn ending at residues 110 or 122-140. The presence of abnormal neurites containing ␣-syn119 in AD without conventional Lewy pathology suggests that AD and Lewy body disease may be more closely related than previously thought.

show abstract

“…Plaque burden was calculated by multiplying this percentage by the area covered by the grid. To confirm the presence of ß-amyloid plaques, thioflavine S was used to stain floating sections in a 1% thioflavine S aqueous solution for 5 minutes, and then differentiated in 70% alcohol 3-5 minutes (Guntern et al 1992, Dong et al 2004). …”

Section: ß-Amyloid Plaque Quantificationmentioning

confidence: 99%

Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer’s disease

Dong¹,

Csernansky

Martin³

et al. 2005

Psychopharmacology

104

View full text Add to dashboard Cite

Rationale: Acetylcholinesterase inhibitors are widely used for the treatment of patients with Alzheimer's disease (AD). However, the relationship between the capacity of such drugs to ameliorate the symptoms of AD and their ability to alter the underlying disease process is not well understood. Transgenic mice that overexpress the human form of amyloid precursor protein and develop deposits of b-amyloid (Ab) and behavioral deficits during adulthood are useful for investigating this question. Objectives: The effects of administration of two acetylcholinesterase inhibitors, physostigmine and donepezil, on Ab plaque formation and memory-related behaviors were investigated in the Tg2576 transgenic mouse model of AD. At 9-10 months of age, Tg2576 transgenic (Tg(+)) mice develop Ab plaques and impairments on paradigms related to learning and memory as compared to transgene negative (Tg(-)) mice. Methods: Beginning at 9 months of age, increasing doses of physostigmine (0.03, 0.1, and 0.3mg/kg), donepezil (0.1, 0.3 and 1.0mg/kg) or saline were administered over six weeks to cohorts of Tg(+) and Tg(-) mice. Performance on tests of spatial reversal learning and fear conditioning was evaluated at each drug dose throughout the period of drug administration. After drug administration was completed, the animals were sacrificed and Ab plaque number was quantified. Results: Administration of physostigmine and donepezil improved deficits in contextual and cued memory in Tg(+) mice so that their behaviors became more similar to Tg(-) mice. However, administration of physostigmine and donepezil tended to improve cued memory and deficits in spatial learning in both Tg(+) and Tg(-) mice. Physostigmine administration demonstrated more prominent effects in improving contextual memory than donepezil, while donepezil was more effective than physostigmine in improving deficits in the acquisition of the spatial memory paradigm. Administration of neither drug altered the deposition of Aß plaques. Conclusions: These studies suggest that acetylcholinesterase inhibitors can ameliorate memory deficits in Tg(+) mice without necessarily altering the deposition of Aß plaques. Tg2576 mice may be useful as an animal model to further investigate the mechanisms by which aceytlcholinesterase inhibitors improve cognitive deficits in patients with AD.

show abstract

An improved thioflavine S method for staining neurofibrillary tangles and senile plaques in Alzheimer's disease

Cited by 125 publications

References 14 publications

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.

Abnormal Neurites Containing C-Terminally Truncated α-Synuclein Are Present in Alzheimer's Disease without Conventional Lewy Body Pathology

Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer’s disease

Contact Info

Product

Resources

About