Frontotemporal dementia is the leading cause of “true” A−/T+ profiles defined with Aβ42/40 ratio

Abstract

Abstract Introduction Patients with positive tauopathy but negative Aβ42 (A−T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ42/40 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 Aβ42/40 ratio and “true” A−T+ patients with normal Aβ42/40 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 tauP181 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
• Cerebrospinal fluid biomarkers
• Aβ42/40 ratio
• Aβ42/Aβ40 ratio
• Frontotemporal dementia
• Suspected non Alzheimer's disease pathology (SNAP)