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The metalloprotease ADAMTS4 generates N-truncated Aβ4–x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer’s disease

Walter, Susanne ; Jumpertz, Thorsten ; Hüttenrauch, Melanie ; Ogorek, Isabella ; Gerber, Hermeto ; Storck, Steffen E. ; Zampar, Silvia ; Dimitrov, Mitko ; Lehmann, Sandra ; Lepka, Klaudia ; Berndt, Carsten ; Wiltfang, Jens ; Becker-Pauly, Christoph ; Beher, Dirk ; Pietrzik, Claus U. ; Fraering, Patrick C. ; Wirths, Oliver

In: Acta Neuropathologica, 2019, vol. 137, no. 2, p. 239–257

Brain accumulation and aggregation of amyloid-β (Aβ) peptides is a critical step in the pathogenesis of Alzheimer’s disease (AD). Full-length Aβ peptides (mainly Aβ1–40 and Aβ1–42) are produced through sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. However, studies of autopsy brain samples from AD patients have demonstrated that a...

The Alzheimer’s disease γ-secretase generates higher 42:40 ratios for β-amyloid than for p3 peptides

Siegel, Gabriele ; Gerber, Hermeto ; Koch, Philipp ; Bruestle, Oliver ; Fraering, Patrick C. ; Rajendran, Lawrence

In: Cell Reports, 2017, vol. 19, no. 10, p. 1967–1976

Alzheimer’s disease is characterized by intracerebral deposition of β-amyloid (Aβ). While Aβ40 is the most abundant form, neurotoxicity is mainly mediated by Aβ42. Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases gives rise to full-length Aβ (Aβ1-x) and N-terminally truncated Aβ′ (Aβ11-x) whereas cleavage by α- and γ-secretases leads to the shorter...

The adipocyte differentiation protein APMAP is an endogenous suppressor of Aβ production in the brain

Mosser, Sebastien ; Alattia, Jean-René ; Dimitrov, Mitko ; Matz, Alexandre ; Pascual, Justine ; Schneider, Bernard L. ; Fraering, Patrick C.

In: Human Molecular Genetics, 2015, vol. 24, no. 2, p. 371-382