Currently, there is no biochemical marker clinically available to test for the presence of Alzheimer's disease (AD). Recent studies suggest that the core component of AD-associated neurofibrillary tangles (NFTs), the microtubule-associated protein tau, might be present in CSF. This study focuses on establishing both the presence of tau in CSF and its potential utility in the diagnosis of AD. We obtained CSF from 181 individuals; 71 of these were diagnosed as having probable AD by NINCDS-ADRDA criteria. The remaining 110 individuals were divided into three groups: (1) age-matched demented non-AD patients (n = 25), (2) neurologic controls (n = 59), and (3) other controls (n = 26). We developed a sensitive enzyme-linked immunosorbent tau assay using monoclonal antibodies prepared against recombinant human tau. We confirmed specificity of the antibodies by a combination of immunoprecipitation and immunoblot results. By this assay we measured that the AD population has a mean level of tau 50% greater than the non-AD dementia patients. Comparing AD patients with all other groups, the difference in tau levels as analyzed by one-way ANOVA is highly statistically significant (p < 0.001). Postmortem analysis of two AD patients with high levels of CSF tau revealed a high density of NFTs in the hippocampus. There was no significant correlation between tau and age in the non-AD groups. This study suggests that CSF tau is elevated in AD and might be a useful aid in antemortem diagnosis.

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ApoE*4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater vascular or degenerative damage among subjects with ApoE*4.

CSF levels of tau protein are increased in many patients with Alzheimer's disease (AD). Studies disagree on whether the increase is found in moderate or severe AD to a greater extent than in mild AD, and in two reports there was an inverse correlation between tau levels and cognitive scores. To readdress this question, we measured CSF tau in a group of mildly impaired patients with AD (Mini-Mental State Examination [MMSE] scores > or =20/30) and compared their tau levels with those in age-comparable normal and neurologic controls. We found that the mean level of CSF tau was significantly increased in the AD group compared with the controls, and 29 of 36 patients with AD had levels that exceeded a cutoff determined in a previous study. CSF tau levels did not correlate with MMSE scores. These findings and those of previous studies show that elevated CSF tau levels are found in most patients with AD, occur early in the course of dementia, and may be useful in supporting the diagnosis of AD.

Over the past decade, efforts have been made to assess the positive therapeutic effects of transcranial magnetic stimulation (TMS) by altering the excitability of the brain. We conducted a double-blind, placebo-controlled study to assess the efficacy of right prefrontal slow repetitive TMS in patients with treatment refractory major depression. This pilot study supports the therapeutic potential of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the treatment of refractory major depression. Additional studies will be necessary to assess the efficacy of rTMS with different indices (frequency, intensity, and stimulation site) for major depression and other psychiatric diseases.