Rapidly Progressive Alzheimer's Disease: A Multicenter Update

Article type: Research Article

Authors: Schmidt, Christian^{a; *} | Haïk, Stephane^{b; c; d; e; g} | Satoh, Katsuya^l | Rábano, Alberto^h | Martinez-Martin, Pablo^h | Roeber, Sigrun^k | Brandel, Jean-Philippe^{b; c; d; e} | Calero-Lara, Miguel^j | de Pedro-Cuesta, Jesúsⁱ | Laplanche, Jean-Louis^f | Hauw, Jean-Jaques^g | Kretzschmar, Hans^k | Zerr, Inga^a

Affiliations: [a] National Reference Center for TSE Surveillance, Department of Neurology, Georg-August-University, Goettingen, Germany | [b] AP-HP, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier, Pitié-Salpêtrière, Paris, France | [c] Universitè Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, France | [d] INSERM, U975, Paris, France | [e] CNRS, UMR 7225, Paris, France | [f] Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, AP-HP, Paris, France | [g] Laboratoire de Neuropathologie Raymond Escourolle, Groupe Hospitalier, Pitié-Salpêtrière, AP-HP, Paris, France | [h] Research Unit, Alzheimer Center Reina Sofia Foundation, and CIBERNED, CIEN Foundation, Carlos III Institute of Health, Madrid, Spain | [i] National Centre for Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain | [j] National Centre for Microbiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain | [k] Department of Neuropathology, Ludwig-Maximilian-University Munich, Munich, Germany | [l] Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan

Correspondence: [*] Correspondence to: Dr. Christian Schmidt, Department of Neurology, Georg August University Hospital, Robert-Koch-Str. 40, 37075 Goettingen, Germany. Tel.: +49 (551) 39 6636; Fax: +49 (551) 39 7020, E-mail: cschmid2@gwdg.de.

Abstract: The objective was to characterize a rapidly progressive subtype of Alzheimer's disease (rpAD). Multicenter (France, Germany, Japan, Spain) retrospective analyses of neuropathologically confirmed rpAD cases initially classified as prion disease due to their clinical phenotype were performed. Genetic properties, cerebrospinal fluid biomarkers, neuropathology, and clinical features were examined. Eighty-nine patients were included (median survival 10 months). APOE and PRNP codon 129 genotype distribution paralleled a healthy control group. APOE ε4 homozygosity was absent. Cerebrospinal fluid biomarkers were abnormal, but within a range as expected for classic AD, except for proteins 14-3-3, which were detectable in 42%. Thus, evidence of the existence of rpAD is accumulating. The APOE profile is intriguing, suggesting that this very rapid disease form might represent a distinct subtype of Alzheimer's disease.

Keywords: Alzheimer's disease, heterogeneity, rapid decline

DOI: 10.3233/JAD-2012-120007

Journal: Journal of Alzheimer's Disease, vol. 30, no. 4, pp. 751-756, 2012