Frontotemporal dementia is the leading cause of “true” A−/T+ profiles defined with Aβ(42/40) ratio

INTRODUCTION: Patients with positive tauopathy but negative Aβ(42) (A−T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ(42/40) ratio supersedes Aβ(42) 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 Aβ(42) 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 Aβ(42) 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.