Low-degree trisomy 21 mosaicism promotes early-onset Alzheimer disease

Nuebling, Georg S.; Prix, Catharina; Brendel, Matthias; Beyer, Leonie; Wlasich, Elisabeth; Loosli, Sandra; Barthel, Henryk; Sabri, Osama; Bartenstein, Peter; Voeglein, Jonathan; Danek, Adrian; Rominger, Axel; Edbauer, Dieter; Haass, Christian und Levin, Johannes (2021): Low-degree trisomy 21 mosaicism promotes early-onset Alzheimer disease. In: Neurobiology of Aging, Bd. 103

Abstract

Trisomy-21 mosaicism (mT21) with subclinical intellectual development disorder or physical phenotype has very rarely been associated with early-onset cognitive decline. Notably, early-onset Alzheimer's disease (EOAD) patients' family histories frequently suggest genetic causes other than autosomal-dominant APP/PSEN-1/2 mutations. We present an EOAD patient in his late fifties newly diagnosed with low-degree mT21 (13%/21% blood lymphocytes/ectodermal cells). We applied fluorescence in-situ hybridization to confirm a diagnosis of mT21. Multimodal positron-emission-tomography applying F-18-fluodesoxyglucose (metabolism), F-18-florbetaben (amyloid-beta deposits) and F-18-PI-2620 (tau-deposits) tracers was used to confirm a diagnosis of EOAD according to the ATN-criteria of AD. Initial PET-studies revealed marked cerebral amyloid-beta- and tau-pathology and parietotemporal hypometabolism, confirming EOAD according to the ATN-criteria of AD. A marked cognitive decline was accompanied by an increase in tau pathology in follow-up studies. This is the first case demonstrating that a low-degree APP gene-dose increase suffices to cause EOAD with prominent amyloid-beta/tau pathology. (C) 2021 Elsevier Inc. All rights reserved.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198