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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
Author(s) -
Takeda Masatoshi,
Tanaka Toshihisa,
Arai Hiroyuki,
Sasaki Hidetada,
Shoji Mikio,
Okamoto Koichi,
Urakami Katsuya,
Nakashima Kenji,
Matsubayashi Takeyuki,
Sugita Mitsunori,
Yoshida Hiroshi
Publication year - 2001
Publication title -
psychogeriatrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 32
eISSN - 1479-8301
pISSN - 1346-3500
DOI - 10.1111/j.1479-8301.2001.tb00073.x
Subject(s) - cerebrospinal fluid , medicine , cognitive impairment , gastroenterology , alzheimer's disease , disease , amyloid β , pathology
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 β ‐amyloid (1–42) (A β 42 ) 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 β 42 , 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=18) and Neurological control (NC: n=27) group. Results : Mean levels of A β 42 in CSF were significantly lower in AD (395 pg/mL) than MCI (586 pg/mL;p<0.001), ND (530 pg/mL; p<0.001), CVD (504 pg/mL; p<0.001) and NC (605 pg/mL; p<0.001), respectively. Mean levels of AD unit (tau/A β 42 ) were significantly higher in AD (1.63) than MCI (0.79; p<0.001), ND (0.56; p<0.001), CVD (0.34; p<0.001) and NC (0.19; p<0.001), respectively. Discrimination of AD from other related disorders was significantly improved by the combined assessment of A β 42 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 unit>0.67) of MCI patients who had progressed to AD within a few years was 79% (15/19). Conclusion : The combined measurement of CSF A β 42 and tau is clinically a useful diagnostic marker to discriminate AD at an early stage including MCI from normal aging and other related disorders.