Cerebrospinal Fluid Triplet in the Diagnosis of Alzheimer-Fischer disease

Introduction: Clinical suspicion of a disease with dementia first described by Alzheimer and Fischer can be supported by changes in concentrations of three proteins in the cerebrospinal fluid: an increase in total tau and phosphorylated tau proteins and a decrease in beta-amyloid (so-called cerebrospinal fluid triplet). The aim of this research was to determine normal concentrations and compare them with levels in patients with Alzheimer-Fischer disease and other dementias. Patients and methods: We measured concentrations of cerebrospinal fluid triplet in the laboratory of the AD Center using Enzyme-Linked ImmunoSorbent Assay in 65 neurological patients without cognitive deficit (controls) [Mini-Mental State Examination, median and interquartile range: 29 (28-29) points] and 34 patients with Alzheimer-Fischer disease according to NINCDS-ADRDA criteria [Mini-Mental State Examination 21 (18-23) points]. Cut-off concentrations were determined using an analysis of receiver operating characteristic curves to achieve maximum sensitivity as well as specificity. Results: Patients with Alzheimer-Fischer disease significantly differed from control subjects in the cerebrospinal fluid concentrations of these analytes [median (interquartile range) pg/ml] of these analytes: total tau [Alzheimer-Fischer disease: 575 (273-1168)] vs [NC: 209 (158-276)], phosphorylated tau [Alzheimer-Fischer disease: 65 (42-90)] vs [NC: 33 (26-40)] and beta-amyloid [Alzheimer-Fischer disease: 560 (370-815)] vs [NC: 748 (580-885)]. Cut-off concentrations established by the receiver operating characteristic analyses were associated with these sensitivities/specificities of total tau 334 pg/ml (72 %/85 %), p181-tau 57 pg/ml (62%/95 %) and beta-amyloid 448 pg/ml (38 %/92 %). Ratios of the analytes, with the exception of beta-amyloid/total tau, or normalization of all three analytes relative to the total protein in the CSF were not better than the concentrations alone in the differentiation of both groups. Conclusion: Total tau and the ratio of beta-amyloid/total tau showed the greatest diagnostic value. Results of cerebrospinal fluid triplet testing can support a diagnosis of Alzheimer-Fischer disease but limitations of this investigation have to be considered.