To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although 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 beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

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The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD.

The levels of od-antichymotrypsin (ACT) in cerebrospinal fluid (CSF) from 66 sporadic Alzheimer's disease (AD) patients and 54 normal controls were measured by enzyme immunoassay and compared. There was no correlation (r=0.259, n=54) between the ACTlevel and normal aging. The levels of ACTwere significantly higher in the total ADgroup (p<0.01) than in the normal control group. Dividing AD patients into early onset AD(n=27) and late onset AD groups (n=39), the mean level of CSFACTin the late onset ADgroup was significantly higher than that in the normal control group (p<0.001) and that in the early onset AD group (p<0.01). Thus, the level of ACTin CSF is closely associated with late onset AD. (Internal Medicine 34: 481-484, 1995)

The Mini-Mental State examination (MMSE) is frequently used to assess the cognitive function of neurological patients. The purpose of this study was to investigate associations between regional cerebral blood flow (rCBF) and MMSE scores in Alzheimer's disease (AD) and localization of cognitive functions. Fifty-nine patients with probable AD (21 males and 38 females; mean age 74 years) and 12 normal volunteers (five males and seven females; mean age 73 years) were studied. CBF was measured by SPECT using the N-isopropyl-p-[(123)I]iodoamphetamine autoradiography method. The CBF images were reconstructed in parallel with the orbitomeatal line and parallel to the long axis of the temporal cortex. Regions of interest were set in the cerebral and cerebellar cortex. Multivariate analysis was performed by the step-wise method, using each section of the MMSE as the dependent variable and the rCBF ratio as the independent variable. The decline in rCBF in the parietal cortex and hippocampus reflected disorientation, and the most significant cortex affecting scores on each section of the MMSE were found to be the anterior temporal cortex for registration, the frontal cortex for attention and calculation, the medial temporal cortex for recall, and the posterior temporal cortex for language.