The added value of Aβ42/Aβ40 in the CSF signature for routine diagnostics of Alzheimer's disease

The cerebrospinal fluid (CSF) signature of Alzheimer's disease (AD) includes abnormal levels of amyloid-beta 1-42 (A beta 42), total tau (t-Tau) and phosphorylated tau (p-Tau). Several studies have reported that the CSF A beta 42/A beta 40 ratio could outperform CSF A beta 42 as a more accurate marker of brain amyloidosis, since it normalizes the CSF A beta 42 levels according to the total production of A beta in the brain. In the present study, we wanted to assess the diagnostic utility of adding the A beta 42/A beta 40 ratio within the core AD CSF biomarkers for the classification of patients, according to NIA-AA criteria and Erlangen score. We consecutively recruited 168 patients (62 with AD and 106 with other neurological diseases) who referred to our Memory Clinic for diagnostic work- up from 2003 to 2016. The use of CSF A beta 42/A beta 40 ratio increased the percentage of correctly diagnosed AD patients from 72.0% to 82.8%. The high gain in sensitivity (from 75.8% to 85.5%) was obtained in face of loss of specificity (from 95.3% to 82.5%). Our study showed that the use of CSF A beta 42/A beta 40 could significantly improve the routine diagnostic work up of AD.