Affiliations: [a] T-cell apoptosis Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Bethesda, MD 20892, USA | [b] Section of Pharmacology and Neuroscience, IST, CBA and Department of Oncology, University of Genova, Genova, Italy | [c] Laboratory of Immunology, NIAID, National Institutes of Health, Bethesda, MD 20892, USA | [d] Cytos Biotechnology AG / ETH Zurich, Wagistrasse 21, CH-8952, Zurich-Schlieren, Switzerland | [e] Istituto di Anatomia Umana and Diparti-mento di Neuroscienze, Università di Genova, via De Toni 10, 16132 Genova, Italy | [f] Albert Einstein College of Medicine, Department of Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Correspondence:
[*]
Corresponding author: Luciano D'Adamio, Albert Einstein College of Medicine, Department of Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA; E-mail: [email protected]
Note: [1] B.P. and L.P. have equally contributed to this work.
Abstract: The amyloid ß protein precursor (AßPP) is sequentially processed by ß- and γ-secretases to generate the Aß peptide. The biochemical path leading to Aß formation has been extensively studied since extracellular aggregates of amyloidogenic forms of Aß peptide (Aß42) are considered the culprit of Alzheimer's disease. Aside from its pathological relevance, the biological role of AßPP proteolysis is unknown. Although never previously described, cleavage of AßPP by γ-secretase should release, together with Aß, a COOH-terminal AßPP Intracellular Domain, herein termed AID. We have now identified AID-like peptides in brain tissue of normal control and patients with sporadic Alzheimer's disease and demonstrate that AID acts as a positive regulator of apoptosis. Thus, overproduction of AID may add to the toxic effect of Aß42 aggregates and further accelerate neurodegeneration.
