Research Paper Volume 12, Issue 1 pp 1011—1033
Down syndrome and Alzheimer's disease: common molecular traits beyond the amyloid precursor protein
- 1 Laboratory of Neuroprotection and Autophagy, Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile
- 2 Departamento de Bioquímica y Biología Molecular and Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
- 3 Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- 4 CIBQA, Universidad Bernardo O’Higgins, Santiago, Chile
- 5 Centro de Modelamiento Molecular, Biofísica y Bioinformática (CM2B2), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
- 6 Center for Exercise, Metabolism, and Cancer Studies (CEMC), Facultad de Medicina, Universidad de Chile, Santiago, Chile
- 7 Autophagy Research Center, Universidad de Chile, Santiago, Chile
- 8 Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile
received: October 2, 2019 ; accepted: December 25, 2019 ; published: January 9, 2020 ;https://doi.org/10.18632/aging.102677
How to Cite
Copyright © 2020 Gomez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Alzheimer’s disease (AD) is the most prevalent type of dementia. Down syndrome (DS) is the leading genetic risk factor for Early-Onset AD, prematurely presenting the classic pathological features of the brain with AD. Augmented gene dosage, including the APP gene, could partially cause this predisposition. Recent works have revealed that alterations in chromosome location due to the extra Chromosome 21, as well as epigenetic modifications, could promote changes in gene expression other than those from Chromosome 21. As a result, similar pathological features and cellular dysfunctions in DS and AD, including impaired autophagy, lysosomal activity, and mitochondrial dysfunction, could be controlled beyond APP overexpression. In this review, we highlight some recent data regarding the origin of the shared features between DS and AD and explore the mechanisms concerning cognitive deficiencies in DS associated with dementia, which could shed some light into the search for new therapeutic targets for AD treatment.
Aβ: Amyloid-β; AD: Alzheimer’s Disease; APP: Amyloid Protein Precursor; BACE1: β-Secretase 1; BACE2: β-Secretase 2; Chr21: Chromosome 21; CNS: Central Nervous System; CSF: cerebrospinal fluid; DS: Down’s Syndrome; EOAD: Early-Onset Alzheimer’s Disease; FAD: Familial Alzheimer’s Disease; IDE: Insulin-Degrading Enzyme; iPSC: induced Pluripotent Stem Cells; GEDD: Gene Expression Dysregulated Domains; lncRNAs: long non-coding RNAs; LOAD: Late-Onset Alzheimer’s Disease; MAPT: Microtubule-Associated Protein Tau; miRNAs: microRNAs; mPTP: mitochondrial Permeability Transition Pore; mtDNA: mitochondrial DNA; ncRNAs: non-coding RNAs; NFTs: Neurofibrillary Tangles; PSEN1: presenilin 1; PSEN2: presenilin 2; ROS: Reactive Oxygen Species.