Frontotemporal dementia is the leading cause of "true" A-/T+ profiles defined with Aβ42/40 ratio

Hélène Pouclet-Courtemanche; Tri-Bao Nguyen; Emilie Skrobala; Claire Boutoleau-Bretonnière; Florence Pasquier; Elodie Bouaziz-Amar; Edith Bigot-Corbel; Susanna Schraen; Julien Dumurgier; Claire Paquet; Thibaud Lebouvier

doi:10.1016/j.dadm.2019.01.001

Frontotemporal dementia is the leading cause of "true" A-/T+ profiles defined with Aβ_42/40 ratio

Alzheimers Dement (Amst). 2019 Feb 15:11:161-169. doi: 10.1016/j.dadm.2019.01.001. eCollection 2019 Dec.

Affiliations

¹ CHU Nantes, Inserm CIC04, Department of Neurology, Centre Mémoire de Ressources et Recherche, Nantes, France.
² CH Delafontaine, Saint-Denis, France.
³ CHU Lille, DISTALZ, Lille, France.
⁴ University of Lille, Inserm U1171, CHU Lille, DISTALZ, Lille, France.
⁵ Département de Biochimie et de biologie moléculaire GH Saint-Louis/Lariboisière/Fernand Widal - Site Lariboisière, AP-HP, Paris, France.
⁶ Inserm UMR-S 1144 Universités Paris Descartes - Paris Diderot Variabilité de Réponse aux Psychotropes, Paris, France.
⁷ CHU de Nantes, Laboratory of Biochemistry, Nantes, France.
⁸ University of Lille, Inserm U1172, CHU Lille, DISTALZ, Lille, France.
⁹ Cognitive Neurology Center, Lariboisiere - Fernand Widal Hospital, AP-HP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Abstract

Introduction: Patients with positive tauopathy but negative Aβ₄₂ (A-T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ_42/40 ratio supersedes Aβ₄₂ and reintegrates "false" A-T+ patients into the Alzheimer's disease spectrum. However, the biomarker and clinical characteristics of "true" and "false" A-T+ patients remain elusive.

Methods: Among the 509 T+N+ patients extracted from the databases of three memory clinics, we analyzed T+N+ patients with normal Aβ₄₂ and compared "false" A-T+ with abnormal Aβ_42/40 ratio and "true" A-T+ patients with normal Aβ_42/40 ratio, before CSF analysis and at follow-up.

Results: 24.9% of T+N+ patients had normal Aβ₄₂ levels. Among them, 42.7% were "true" A-T+. "True" A-T+ had lower CSF tau^P181 than "false" A-T+ patients. 48.0% of "true" A-T+ patients were diagnosed with frontotemporal lobar degeneration before CSF analysis and 64.0% at follow-up, as compared with 6% in the "false" A-T+ group (P < .0001).

Discussion: Frontotemporal lobar degeneration is probably the main cause of "true" A-T+ profiles.

Keywords: Alzheimer's disease; Aβ42/40 ratio; Aβ42/Aβ40 ratio; Cerebrospinal fluid biomarkers; Frontotemporal dementia; Suspected non Alzheimer's disease pathology (SNAP).