title: Intraneuronal Aβ as a trigger for neuron loss: can this be translated into human pathology?
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.affiliation: Division of Molecular Psychiatry, University Medicine Göttingen, von-Siebold-Strasse 5, 37075 Göttingen, Germany. tbayer@gwdg.de
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D011761:Pyrrolidonecarboxylic Acid