CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment

Standard markers in cerebrospinal fluid (CSF), as soluble amyloid beta 1-42 (Aβ1-42) and total tau protein (t-tau), may contribute to dementia subtypes diagnostic accuracy. Yet, their sensitivity to assess the different degree of cognitive deficit is not fully clarified. Our study analyses Aβ1-42 and t-tau CSF levels in different cohorts of Alzheimer's disease (AD) patients, distinguished as early AD (mild cognitively impaired subjects recently converted to AD), mild AD (MMSE <23; ≥ 18), and moderately advanced AD (MMSE <18). The control group was represented by age-matched patients affected by depressive pseudo-dementia. Reduced Aβ1-42 and increased t-tau CSF levels were confirmed as hallmarks of AD at any disease stage. In early AD patients, Aβ1-42 levels were already significantly low, if compared to the control group (336 vs 867 ng/L; p <0.0001). On the contrary, Aβ1-42 levels did not differ between AD subgroups, and in particular between mild to moderate AD. A significant progressive increase of t-tau concentration was found when comparing early AD (269 ng/L) to more advanced AD stages (468 ng/L and 495 ng/L for mild and moderate AD, respectively). Our findings confirm that the impairment of amyloidogenic cascade is an early, even pre-clinical process, but suggest that soluble Aβ1-42 concentration has a negligible correlation with the clinical progression. Conversely, t-tau concentration correlates with the transition towards marked cognitive impairment.