AD with subcortical white matter lesions and vascular dementia: CSF markers for differential diagnosis

We investigated whether the cerebrospinal fluid (CSF) biomarkers beta-amyloid 1-42 (Aβ1-42), total tau (t-tau) protein and tau protein phosphorylated at threonine 181 (p-tau181) could discriminate Alzheimer's disease (AD) from vascular dementia (VD) patients. CSF samples of Aβ1-42, t-tau, and p-tau181 were collected from probable AD (n = 35), probable AD with white matter changes (WMC) indicative of concomitant cerebrovascular disorder (CVD, n = 31), VD (n = 20), and an age-matched subgroup of patients with other neurological disorders (OND) without cognitive impairment (n = 24). AD patients showed very low Aβ1-42 levels (median = 393 pg/ml). Aβ1-42, but not t-tau, differentiated AD from VD patients. However, the markers did not discriminate AD vs. AD plus WMC. In particular, both subgroups showed similar CSF biomarkers but they were significantly different from VD. ROC analysis showed that Aβ1-42 could discriminate AD from VD (AUC = 0.85). The cutoff of 493 pg/ml gave sensitivity and specificity values of 77% and 80%, respectively. Similar results were obtained when Aβ1-42 was employed to discriminate AD with WMC from VD (95% specificity and 60% sensitivity, but with cutoff of 750 pg/ml). T-tau increased aspecifically in all cognitively impaired patients. P-tau181 performed better than t-tau in discriminating AD (with or without WMC) vs. VD. In conclusion, Aβ1-42 proved to be a valuable tool to discriminate AD vs. VD patients and possibly to improve diagnostic accuracy in clinical forms, improperly classified as "mixed dementia" based on radiological vascular lesions.