Basic and Clinical Studies on the Measurement of β‐amyloid_(1–42) in Cerebrospinal Fluid as a Diagnostic Marker for Alzheimer's Disease and Related Disorders: Multi Center Study in Japan

Abstract

Background: The development of diagnostic markers for earlier and more accurate clinical diagnosis of Alzheimer's disease (AD) is essential to identify unequivocally AD patients during life. This study is to investigate the basic performance and clinical significance of P-amyloid(142) (AP42) level measurement in cerebrospinal fluid (CSF) alone or in combination with CSF tau for distinguishing AD from non-AD disorders. Methods: The basic characteristics of the reagent for measuring A&, which used Sandwich ELISA, was examined. The clinical studies were done at 5 centers in Japan. CSF samples from 353 patients were collected and classified into the following six groups; AD (n=189), Mild Cognitive Impairment (MCI: n=25), Neurodegenerative disorders without AD (ND: n=66), Cerebrovascular disturbance (CVD: n=28), Other neurological disorders (OND: n=l8) and Neurological control (NC: n=27) group. Results: Mean levels of AP42 in CSF were significantly lower in AD (395 ps/ mL) than MCI (586 pg/mL; peO.OOl), ND (530 pg/mL; peO.OOl), CVD (504 ps/ mL; peO.001) and NC (605 pg/mL; peO.OOl), respectively. Mean levels of AD unit ( t a~/ A p~~) were significantly higher in AD (1.63) than MCI (0.79; peO.OOl), ND (0.56; peO.OOl), CVD (0.34; peO.001) and NC (0.19; peO.OOl), respectively. Discrimination of AD from other related disorders was significantly improved by the combined assessment of AP4* and tau. When the cut-off level of an AD unit was 0.67, the sensitivity for AD was 80% and the specificity for other related disorders was 86%. The positive rate (AD unib0.67) of MCI patients who had progressed to AD within a few years was 79% (1 511 9). Conclusion: The combined measurement of CSF AP42 and tau is clinically a useful diagnostic marker to discriminate AD at an early stage including MCI from normal aging and other related disorders.

Effects of Processing and Storage Conditions on Amyloid β (1–42) and Tau Concentrations in Cerebrospinal Fluid: Implications for Use in Clinical Practice

“…An explanation for this finding could be that binding of A␤42 to albumin masked the epitope recognized by A␤42-specific antibodies (15,16 ). This binding of A␤42 to other proteins might also cause the low recovery rate of the A␤42 ELISA, although Vanderstichele et al (6 ) and others could not find interference with A␤ by other proteins, including albumin (17 ). However, interference experiments are largely dependent on the protocol being used or on whether preincubation is needed.…”

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

“…Most studies have found normal to mildly increased CSF T-tau levels in other dementias, such as frontotemporal dementia (FTD) 14,15,21,50,52,69,70,73,[82][83][84][85][86] and Lewy body dementia (LBD). [85][86][87][88][89][90] Other than in aged nondemented individuals, normal CSF T-tau is found in depression, alcoholic dementia, and in chronic neurological disorders such as Parkinson's disease (PD) and progressive supranuclear palsy.…”

Efficacy of combination treatment of fluvoxamine and tiapride for repetitive behaviors in frontotemporal lobar degeneration

“…He was diagnosed as having frontotemporal dementia (FTD) in FTLD because of his disinhibited, stereotyped and repetitive behaviors, the pattern of cognitive dysfunction, and neuroimaging findings. The result of CSF tau and Aβ (tau/Aβ) did not indicate that he had AD 5 …”

“…Neurologic examination was unremarkable except for the grasp reflexes of both hands. In the cerebral spinal fluid (CSF) general findings were normal and the levels of Tau, Aβ 42 and Tau/Aβ 42 were 244 pg/mL, 827 pg/mL and 0.30, respectively (Tau/Aβ 42 in patients with Alzheimer's disease (AD) is 1.63 ± 1.32 and in neurodegenerative disorders without AD (ND) is 0.56 ± 0.63) 5 . Electroencephalogram (EEG) was normal.…”