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Intraneuronal Aβ as a trigger for neuron loss: can this be translated into human pathology?
Biochem Soc Trans 2011; 39(4):857-61BS

Abstract

In the present review, we summarize the current achievements of modelling early intraneuronal Aβ (amyloid β-peptide) accumulation in transgenic mice with the resulting pathological consequences. Of special importance will be to discuss recent developments and the translation of the results to AD (Alzheimer's disease). N-terminally truncated AβpE3 (Aβ starting with pyroglutamate at position 3) represents a major fraction of all Aβ peptides in the brain of AD patients. Recently, we generated a novel mAb (monoclonal antibody), 9D5, that selectively recognizes oligomeric assemblies of AβpE3 and demonstrated the potential involvement of oligomeric AβpE3 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 non-detectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal staining was observed. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall Aβ levels and stabilized behavioural deficits. In summary, we have demonstrated that intraneuronal Aβ is a valid risk factor in model systems and AD patients. This feature of AD pathology was successful in identifying novel low-molecular-mass oligomeric Aβ-specific antibodies for diagnosis and therapy.

Authors+Show Affiliations

Division of Molecular Psychiatry, University Medicine Göttingen, von-Siebold-Strasse 5, 37075 Göttingen, Germany. tbayer@gwdg.deNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21787313

Citation

Bayer, Thomas A., and Oliver Wirths. "Intraneuronal Aβ as a Trigger for Neuron Loss: Can This Be Translated Into Human Pathology?" Biochemical Society Transactions, vol. 39, no. 4, 2011, pp. 857-61.
Bayer TA, Wirths O. Intraneuronal Aβ as a trigger for neuron loss: can this be translated into human pathology? Biochem Soc Trans. 2011;39(4):857-61.
Bayer, T. A., & Wirths, O. (2011). Intraneuronal Aβ as a trigger for neuron loss: can this be translated into human pathology? Biochemical Society Transactions, 39(4), pp. 857-61. doi:10.1042/BST0390857.
Bayer TA, Wirths O. Intraneuronal Aβ as a Trigger for Neuron Loss: Can This Be Translated Into Human Pathology. Biochem Soc Trans. 2011;39(4):857-61. PubMed PMID: 21787313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intraneuronal Aβ as a trigger for neuron loss: can this be translated into human pathology? AU - Bayer,Thomas A, AU - Wirths,Oliver, PY - 2011/7/27/entrez PY - 2011/7/27/pubmed PY - 2011/11/16/medline SP - 857 EP - 61 JF - Biochemical Society transactions JO - Biochem. Soc. Trans. VL - 39 IS - 4 N2 - In the present review, we summarize the current achievements of modelling early intraneuronal Aβ (amyloid β-peptide) accumulation in transgenic mice with the resulting pathological consequences. Of special importance will be to discuss recent developments and the translation of the results to AD (Alzheimer's disease). N-terminally truncated AβpE3 (Aβ starting with pyroglutamate at position 3) represents a major fraction of all Aβ peptides in the brain of AD patients. Recently, we generated a novel mAb (monoclonal antibody), 9D5, that selectively recognizes oligomeric assemblies of AβpE3 and demonstrated the potential involvement of oligomeric AβpE3 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 non-detectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal staining was observed. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall Aβ levels and stabilized behavioural deficits. In summary, we have demonstrated that intraneuronal Aβ is a valid risk factor in model systems and AD patients. This feature of AD pathology was successful in identifying novel low-molecular-mass oligomeric Aβ-specific antibodies for diagnosis and therapy. SN - 1470-8752 UR - https://www.unboundmedicine.com/medline/citation/21787313/Intraneuronal_Aβ_as_a_trigger_for_neuron_loss:_can_this_be_translated_into_human_pathology L2 - http://www.biochemsoctrans.org/cgi/pmidlookup?view=long&pmid=21787313 DB - PRIME DP - Unbound Medicine ER -