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Find video protocols related to scientific articles indexed in Pubmed.
Identification of low molecular weight pyroglutamate A{beta} oligomers in Alzheimer disease: a novel tool for therapy and diagnosis.
J. Biol. Chem.
PUBLISHED: 10-22-2010
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N-terminally truncated A? peptides starting with pyroglutamate (A?pE3) represent a major fraction of all A? peptides in the brain of Alzheimer disease (AD) patients. A?pE3 has a higher aggregation propensity and stability and shows increased toxicity compared with full-length A?. In the present work, we generated a novel monoclonal antibody (9D5) that selectively recognizes oligomeric assemblies of A?pE3 and studied the potential involvement of oligomeric A?pE3 in vivo using transgenic mouse models as well as human brains from sporadic and familial AD cases. 9D5 showed an unusual staining pattern with almost nondetectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal and blood vessel staining was observed. Using a novel sandwich ELISA significantly decreased levels of oligomers in plasma samples from patients with AD compared with healthy controls were identified. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall A? plaque load and A?pE3 levels, and normalized behavioral deficits. These data indicate that 9D5 is a therapeutically and diagnostically effective monoclonal antibody targeting low molecular weight A?pE3 oligomers.
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CALHM1 P86L polymorphism does not alter amyloid-beta or tau in cerebrospinal fluid.
Neurosci. Lett.
PUBLISHED: 10-22-2009
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Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimers disease (AD). Moreover, the risk allele increased amyloid-beta (A beta) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate A beta or tau levels in cerebrospinal fluid (CSF). Nearly 200 individuals with AD or other cognitive disorders were included for CSF analysis and CALHM1 genotyping. No significant differences in CSF levels of A beta 42, tau or phospho-tau were found across the various CALHM1 genotypes. In conclusion, we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated AD biomarkers.
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Reduced levels of IgM autoantibodies against N-truncated pyroglutamate A? in plasma of patients with Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 05-11-2009
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In the present work, we investigated the level of IgM autoantibodies directed against different A? epitopes as potential diagnostic biomarker for Alzheimers disease (AD). Anti-A? autoantibody levels were measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To validate the presence of anti-A? IgMs, pooled plasma samples were subjected to gel-filtration analysis. The mean level of pGluA?-IgM (N-terminal truncated starting at position three with pyroglutamate) was significantly decreased in AD patients as compared to HC. In the group of MCI patients there was a significant positive correlation between pGluA?-IgM and cognitive decline analyzed by MMSE (rho = 0.58, d.f. = 13, p = 0.022). These observations indicate that the level of IgM autoantibodies against pGluA? is a promising plasma biomarker for AD and correlates with the cognitive status of individuals at risk to develop AD.
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Oligomerization partially explains the lowering of Abeta42 in Alzheimers disease cerebrospinal fluid.
Neurodegener Dis
PUBLISHED: 03-16-2009
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The lowering of natively analyzed Abeta42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimers disease (AD). The presence of Abeta oligomers can interfere with such analyses causing underestimation of Abeta levels due to epitope masking. The aim was to investigate if the lowering of CSF Abeta42 seen in AD is caused by oligomerization.
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Circulating immune complexes of Abeta and IgM in plasma of patients with Alzheimers disease.
J Neural Transm
PUBLISHED: 01-23-2009
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It has previously been shown that immune complexes (IC) of a given biomarker with class M immunoglobulins (IgM) provide better performances compared to the unbound biomarker in a number of cancer entities. In the present work, we investigated IC of IgM-Abeta as a potential biomarker for Alzheimers disease (AD). Abeta-IgM concentration has been measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To characterize the fractions associated with Abeta, pooled plasma samples were subjected to gel-filtration analysis. Size-separated fractions were analyzed for the presence of Abeta using a sandwich ELISA assay. A strong reactivity was observed in the high molecular weight IgM (>500 kDa) and 150 kDa (IgG) fractions indicating that blood Abeta is strongly associated with antibodies. Using an ELISA assay detecting Abeta-IgM complexes, we observed that high levels of Abeta-IgMs were detectable in HC and MCI patients; however, there was no significant difference to the AD group.
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Genetic analysis of Alzheimers disease in the Uppsala Longitudinal Study of Adult Men.
Dement Geriatr Cogn Disord
PUBLISHED: 01-14-2009
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Genetic factors influencing common complex conditions have proven difficult to identify, and data from numerous investigations have provided incomplete conclusions as to the identity of these genes. Here we aimed to identify susceptibility genes for late-onset Alzheimers disease (AD).
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.