Details

Autor(en) / Beteiligte

• Sergeant, Nicolas
• Bombois, Stepanie
• Ghestem, Antoine
• Drobecq, Hervé
• Kostanjevecki, Vesna
• Missiaen, Carla
• Wattez, Annick
• David, Jean‐Phillipe
• Vanmechelen, Eugeen
• Sergheraert, Christian
• Delacourte, André

Titel

Truncated beta‐amyloid peptide species in pre‐clinical Alzheimer's disease as new targets for the vaccination approach

Ist Teil von

• Journal of neurochemistry, 2003-06, Vol.85 (6), p.1581-1591

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2003

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Vaccination against human beta‐amyloid peptide (Aβ) has been shown to remove the amyloid burden produced in transgenic mice overexpressing the mutated human amyloid precursor protein (APP) gene. For human beings, the efficiency of this therapeutic strategy has to take into account the specificities of human amyloid, especially at the early stages of ‘sporadic’ Alzheimer's disease (AD). Aβ 40/42 were previously quantified in tissues from our well‐established brain bank, including non‐demented individuals with both mild amyloid and tau pathologies, hence corresponding to the earliest stages of Alzheimer pathology. Herein, we have adapted a proteomic method combined with western blotting and mass spectrometry for the characterization of insoluble Aβ extracted in pure‐formic acid. We demonstrated that amino‐truncated Aβ species represented more than 60% of all Aβ species, not only in full blown AD, but also, and more interestingly, at the earliest stage of Alzheimer pathology. At this stage, Aβ oligomers were exclusively made of Aβ‐42 species, most of them being amino‐truncated. Thus, our results strongly suggest that amino‐truncated Aβ‐42 species are instrumental in the amyloidosis process. In conclusion, a vaccine specifically targeting these pathological amino‐truncated species of Aβ‐42 are likely to be doubly beneficial, by inducing the production of specific antibodies against pathological Aβ products that are, in addition, involved in the early and basic mechanisms of amyloidosis in humans.