N-terminal EFRH sequence of Alzheimer's β-amyloid peptide represents the epitope of its anti-aggregating antibodies

Frenkel, Dan; Balass, Moshe; Solomon, Beka

doi:10.1016/s0165-5728(98)00098-8

Cited by 90 publications

(46 citation statements)

References 12 publications

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“…These data indicate that mouse and guinea pig antibodies recognized the same epitope, composed of four amino acid residues corresponding to positions 3-6 in the A␤P, similar to the antiaggregating antibodies previously investigated (9).…”

Section: ϫ6supporting

confidence: 77%

“…To select the phages containing EFRH peptide epitope, we screened the phage-epitope library with biotinylated antibody (9). After three cycles of panning and phage amplification, ELISA analysis revealed that of the phage clones, most (above 90%) bound specifically to the antibody.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, such antibodies were found to prevent the formation of fibrillar ␤-amyloid (8). Using a phage-peptide library composed of filamentous phage displaying random combinatorial peptides, we previously defined the EFRH residues located at positions 3-6 of the N-terminal A␤P as the epitope of anti-aggregating antibodies within A␤P (9,10). Locking of this epitope by antibodies modulates the dynamics of aggregation as well as resolubilization of already formed aggregates (7,8).…”

mentioning

confidence: 99%

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Immunization against Alzheimer's β-amyloid plaques via EFRH phage administration

Frenkel

Katz

Solomon

2000

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

157

103

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The epitope EFRH, corresponding to amino acids 3-6 within the human ␤-amyloid peptide (A␤P), acts as a regulatory site controlling both the formation and disaggregation process of the ␤-amyloid fibrils (A␤). Locking of this epitope by highly specific antibodies affects the dynamics of the entire A␤P molecule, preventing selfaggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human A␤ fibrils into transgenic mice suggests the feasibility of vaccination against Alzheimer's disease. Here, we report the development of an immunization procedure for the production of effective anti-aggregating ␤-amyloid antibodies based on filamentous phages displaying the EFRH peptide as specific and nontoxic antigen. Effective autoimmune antibodies were obtained by EFRH phage administration in guinea pigs, which exhibit A␤P identical to the human A␤P region. Moreover, because of the high antigenicity of the phage, no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies after a short immunization period of 3 weeks. Availability of such antibodies opens up possibilities for the development of an efficient and long-lasting vaccination for the prevention and treatment of Alzheimer's disease.Alzheimer's disease ͉ ␤-amyloid ͉ vaccine ͉ EFRH phage ͉ autoantibodies

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Section: ϫ6supporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Immunization against Alzheimer's β-amyloid plaques via EFRH phage administration

Frenkel

Katz

Solomon

2000

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

157

103

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“…A passive anti-A␤ immunotherapy will likely be most beneficial by targeting multiple A␤1-42 assemblies, including soluble oligomers , and other A␤ peptide aggregates that contribute to early events in the A␤1-42 oligomerization process (Frenkel et al, 1998;Lambert et al, 1998;Lee et al, 2006;Spires-Jones et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

An Effector-Reduced Anti- -Amyloid (A ) Antibody with Unique A Binding Properties Promotes Neuroprotection and Glial Engulfment of A

Adolfsson¹,

Pihlgren²,

Toni³

et al. 2012

Journal of Neuroscience

265

241

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“…The same group also showed the similar catalytic activity of the antibody towards fibrillar Aβ assembly [22][23][24]. Furthermore, they also showed that anti-aggregating antibodies against the EFRH residues located at positions 3-6 of the N-terminal Aβ peptide prevent self-aggregation [25] or resolve preformed aggregates [26] in vitro and in vivo [27].…”

Section: Catalytic Modifications Of Aβ Assemblymentioning

confidence: 78%

Molecular Mechanism Underlying Aβ Immunotherapy: Implications for the Toxic Action of Aβ Oligomers

Matsubara

Takamura²

2013

J Gerontol Geriatric Res

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Aβ immunotherapy brought us not only hope for but also led to greater attention to the mechanism underlying the clearance of amyloid β (Aβ), which provided fascinating insights into disease-relevant molecules such as toxic Aβ oligomers (AβOs). Accumulated lines of evidence indicate that AβOs play a causative role in the pathogenesis of Alzheimer's disease (AD), leading to a synaptic failure, which is considered a major cellular mechanism underlying the cognitive deficits in patients with mild cognitive impairment and AD. In this mini review, we focus on recent knowledge of the possible mechanisms underlying the action of the anti-Aβ antibody to clarify the toxic action of AβOs.

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N-terminal EFRH sequence of Alzheimer's β-amyloid peptide represents the epitope of its anti-aggregating antibodies

Cited by 90 publications

References 12 publications

Immunization against Alzheimer's β-amyloid plaques via EFRH phage administration

Immunization against Alzheimer's β-amyloid plaques via EFRH phage administration

An Effector-Reduced Anti- -Amyloid (A ) Antibody with Unique A Binding Properties Promotes Neuroprotection and Glial Engulfment of A

Molecular Mechanism Underlying Aβ Immunotherapy: Implications for the Toxic Action of Aβ Oligomers

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