A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology.

BACKGROUND: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- ß (Aß), plasma tau, and serum antibodies for Aß1 - 42 are not yet well established. OBJECTIVE: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology. METHODS: With only 1.5µl of serum, we examined a new target plate "BLOTCHIP®" plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains. RESULTS: Apart from Aß or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain Aß deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains. CONCLUSION: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.

Impact of FDG-PET findings on decisions regarding patient management strategies: a multicenter trial in patients with lung cancer and other types of cancer.

OBJECTIVE: To date, numerous studies have been conducted on the diagnostic capabilities of positron emission tomography using [(18)F]-fluorodeoxyglucose (FDG-PET). However, no studies designed to evaluate the influence of FDG-PET on the selection of patient management strategies within the Japanese healthcare system have been reported to date. The aim of the present study was to investigate prospectively the proportion of patients whose management strategies were modified based on FDG-PET findings (strategy modification rate). METHODS: The strategy modification rate was calculated by comparing the patient management strategy (test and treatment plans) after FDG-PET with the strategy before FDG-PET for 560 cancer patients with nine types of cancer (lung cancer, breast cancer, colorectal cancer, head/neck cancer, brain tumor, pancreas cancer, malignant lymphoma, cancer of unknown origin, and melanoma). In addition, the details of the modifications to the patient management strategies were analyzed. RESULTS: The strategy modification rate for patients with lung cancer was 71.6% (149 of 208 patients, 95% confidence interval 65.0-77.7%), which was higher than previously reported strategy modification rates for lung cancer before and after FDG-PET (25.6%). The strategy modification rates for patients with cancers other than lung cancer were as follows: breast, 44.4% (56/126); colorectal, 75.6% (62/82); head and neck, 65.2% (15/23); malignant lymphoma, 70.0% (35/50); pancreas, 85.0% (17/20); and cancer of unknown origin, 78.0% (32/41). The mean modification rate (major and minor modifications) of the treatment plans after FDG-PET, relative to the plans before FDG-PET, was 55.4% (range 44.0-69.2%), with major modifications pertaining to the treatment plan made in 43.3-68.2% of the patients based on the objectives of the FDG-PET examination. CONCLUSIONS: The results from this study indicate that FDG-PET can contribute to the modification of management strategies (particularly treatment plans), especially for lung cancer patients but also for patients with other types of cancer.

TT virus-positive hepatocellular carcinoma arising from non-cirrhotic liver in an elderly man.

A 43-mm hepatic tumor was incidentally detected by computed tomography in a 72-year-old man. Liver function test results were normal. Serum hepatitis B, C and G viruses were negative, while serum TT virus was positive. Autoantibodies were negative. The patient had no history of alcohol consumption. The tumor was found to be a moderately differentiated hepatocellular carcinoma (HCC) from a resected specimen. Neither lobular inflammation nor fibrosis was observed in the surrounding liver. Intrahepatic hepatitis B virus was not detected. This is a case of non-B, non-C HCC positive for only TT virus arising from a non-cirrhotic liver.