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 (MMSEb23; ≥18), and moderately advanced AD (MMSEb18). 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; pb0.0001). 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.