Cerebrospinal fluid and serum autoantibodies against neurocytoskeletal proteins in patients with Alzheimer's disease

Abstract

states. The optimalprocess of clinical assessmentmay includemultiple technologies such as neuropsychological assessment, neuroimaging, and fluid biomarker analysis, each used at appropriate time points in a staged diagnostic pathway. EDAR is a Europe-wide prospective longitudinal study assessing the potential for CSF and other biomarkers, including cognition, in the early diagnosis of AD. Methods: Patients with mild cognitive impairment, AD and other dementias and healthy elderly controls (total n 1⁄4 144) were recruited from seven centres across Europe. Memory, attention and executive functions were assessed using the Cambridge Neuropsychological Test Battery (CANTAB). Cerebrospinal fluid was obtained on a single occasion and assayed using Luminex for As1-42, total tau and hyperphosphorylated tau. Results: Lower CSF As1-42 levels were associated with poorer performance on CANTAB paired associates learning (rho1⁄4 -.3, p< .001) and spatial working memory (rho1⁄4-.3, p1⁄4 .002) tests, andwith slower (rho1⁄4-.3, p1⁄4 .001) andmore variable (rho1⁄4-.4, p< .001) choice reaction time. The tau:As1-42 ratiowas lower in individuals with better episodic memory and less variable choice reaction time (both rho 1⁄4 .2, p 1⁄4 .01). High P-tau181P levels were associated with faster simple reaction time (rho 1⁄4 -.3, p 1⁄4 .001). CSF biomarker levels appeared unrelated to scores on tests of semantic memory and executive function. Associations between cognitive and CSF biomarkers differed between diagnostic groups. Conclusions: Among healthy and impaired elderly individuals, scores on computerised cognitive tests are correlated with CSF biomarkers of amyloid and tau pathologies.