LONGITUDINAL-STUDY OF CEREBROSPINAL-FLUID LEVELS OF TAU, A-BETA-1-40,AND A-BETA-1-42(43) IN ALZHEIMERS-DISEASE - A STUDY IN JAPAN

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta 1-42(43) in the cerebrospinal fluid (CSF) that accompany no rmal aging and the progression of Alzheimer's disease (AD), CSF sample s of 93 AD patients, 32 longitudinal subjects among these 93 AD patien ts, 33 patients with non-AD dementia, 56 with other neurological disea ses, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Althoug h the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta 1-42(43) levels and a significant increase of the ratio of A beta 1-4 0 to A beta 1-42(43) were observed in the AD patients. The longitudina l AD study showed continuous low A beta 1-42(43) levels and an increas e of the ratio of A beta 1-40 to A beta 1-42(43) before the onset of A D. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta 1-42(43) and the ratio of A beta 1-40 to A beta 1-42(43) may star t at early stages in AD. The assays of CSF tau, A beta 1-40, and A bet a 1-42(43) provided efficient diagnostic sensitivity (71%) and specifi city (83%) by using the production of tau levels and the ratio of A be ta 1-40 to A beta 1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.