We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/phospho-tau199) by a recently established sandwich ELISA. The CSF/phospho-tau199 levels in the AD group were significantly elevated compared to those in all the other non-AD groups. Receiver operating characteristics curves showed that the diagnostic sensitivity and specificity for the AD group vs all the other non-AD groups using the CSF/phospho-tau199 were 85.2% and 85.0%, respectively. Furthermore, there was a significant positive correlation between CSF/phospho-tau199 and CSF/total-tau levels in the AD group. Elevated CSF/phospho-tau199 in the AD group was noted irrespective of age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we suggest that CSF/phospho-tau199 may be a novel and logical biomarker in supporting antemortem diagnosis of AD.

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A new technique is proposed for NMR image restoration from the influence of main magnetic field non-uniformities. This technique is applicable to direct Fourier NMR imaging. The mathematical basis and details of this technique are fully described. Modification to include image restoration from non-linear field gradient influence is also presented. Computer simulation demonstrates the effectiveness of this technique for both Fourier zeugmatography and spin-warp imaging.

Summary:Correlations between Tl and T2 relaxation times and water and electrolyte content in the normal and ischemic rat and gerbil brains were studied by means of both nuclear magnetic resonance (NMR) spectroscopic and imaging methods. In the spectroscopic experiment on excised rat brains, Tl was linearly dependent on tissue water content and T2 was prolonged in edematous tissue to a greater extent than expected by an increase in water content, showing that T2 possesses a greater sensi tivity for edema identification and localization. Changes in Na + and K + content of the tissue mattered little in the prolongation of relaxation times. Serial NMR imaging of gerbil brains insulted with permanent hemispheric isch- Proton nuclear magnetic resonance (NMR)imaging enables sensitive detection of cerebral ischemia within several hours after the onset of dis ease (Buonanno et aI. , 1983; Mano et aI. , 1983; Spetzler et aI. , 1983). T1 (spin-lattice) and T2 (spin-spin) relaxation times are prolonged in isch emic tissue, and the degree of damage and extent of injury can be pictorialized by NMR imaging. Pro longation of relaxation times is considered to be a result of the development of brain edema (Go and Edzes, 1975; Naruse et aI. , 1982). However, the contrast of the NMR image is arbitrarily controlled by the pulse sequence used. As a consequence, the Abbreviations used: IR, inversion recovery; NMR, nuclear magnetic resonance; PO, proton density; SE, spin echo; SR, sat uration recovery; TE, time to echo; n, time of inversion; TR , time of repetition. 212emia offered early lesion detection in TJ-and especially T2-weighted images (detection as soon as 30 min after insult). The progressive nature of lesions was also imaged. Calculated TJ and T2 relaxation times in regions of interest correlated excellently with tissue water con tent (r = 0.892 and 0.744 for T 1 and T2, respectively). As a result, detection of cerebral ischemia utilizing NMR imaging was strongly dependent on a change in tissue water content. The different nature of Tl and T2 relax ation times was also observed.