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BACKGROUND: The new proposed diagnostic criteria for early diagnosis of Alzheimer's Disease (AD) underline the value of cerebrospinal fluid (CSF) biomarkers. The first aim of the study was to determine the diagnostic accuracy of CSF biomarker Abeta1-42, T-tau, and P-tau in differentiating AD patients in our cohort by means of "pure" biomarkers and in form of a combined analysis of these biomarkers. The second aim of the study was to determine the diagnostic accuracy of these markers for predicting incipient AD in patients with mild cognitive impairment (MCI). METHODS: We studied 102 CSF samples: 33 AD [mean age at baseline 71.2 (54-86)], 16 MCI [mean age at baseline 71.3 (57-78)], 24 non AD dementia, including 7 vascular dementia, 4 frontotemporal degeneration, 5 dementia with Lewy Body, and 8 with other dementia [mean age at baseline 72.7 (51-87)] and 32 non-demented neurological patients [mean age at baseline 71.3 (45-87) referred to as control (CO) later in the text]. A double sandwich ELISA (Innotest beta amyloid Abeta1-42, hTau and P-tau181 by Innogenetics, Gent, Belgium) was performed to quantify the concentration of the above biomarkers. The three biomarkers were then combined in the IATI index [(measured Ab1-42)/(240 + 1.18 *measured tau)], and in the ratios Abeta1-42/T-tau, Abeta1-42/P-tau, T-tau/Abeta1-42 and P-tau/Abeta1-42. RESULTS: Abeta1-42, T-tau and P-tau181 concentration showed statistically significant differences between AD and CO (327.2 pg/mL +/- 150.2 pg/mL and 659.4 pg/mL +/- 254.2 pg/mL; 508.2 pg/mL +/- 360.2 pg/mL and 305.3 pg/mL +/- 228.9 pg/mL; 82.2 pg/mL +/- 26.1 pg/mL and 45.3 pg/mL +/- 26.4 pg/mL, respectively, p < 0.05), while the difference between AD and MCI was statistically different only for Abeta1-42 (327.2 pg/mL +/- 150.2 pg/mL and 600.8 +/- 271.9 pg/mL, respectively, p < 0.05). The IATI index was 0.5 +/- 0.3 in AD, 0.9 +/- 0.6 in MCI, 1.37 +/- 0.9 in non AD dementia and 1.26 +/- 0.8 in non-demented neurological patients. With a cut-off fixed at 1 the sensitivity and specificity of the IATI index in discriminating AD from CO was 84% and 52%, respectively. CONCLUSIONS: This study confirms the great significance of CSF biomarker measurements in AD diagnosis in clinical routine. It is understood that a clinical diagnostic work-up is necessary in the process. Moreover, a biochemical profile of CSF biomarkers requires further investigations.

The frequency and risk factors for intracerebral haemorrhage (ICH) after ischemic stroke are well-known. ICH frequency is increased by the use of antithrombotic or thrombolytic drugs. Several experimental studies have demonstrated a relationship between ICH and hypertension after fibrinolysis, but the optimal blood pressure levels in patients treated with recombinant tissue plasminogen activator (rTPA) are as yet unknown. We evaluated the role of blood pressure in patients with ischemic stroke treated with rTPA within 3h of symptom onset. We treated 86 consecutive patients admitted to our stroke unit between 2002 and 2008 and prospectively recorded the clinical and instrumental data in our stroke registry. We evaluated haemorrhagic complications by reviewing imaging findings. Blood pressure was recorded before rTPA and at 6, 12, 18, and 32h. Total cerebral haemorrhage occurred in eleven (12.7%) patients, and symptomatic intracerebral haemorrhage occurred in seven (8.1%). We failed to find a correlation between blood pressure levels and stroke severity at admission. High blood pressure levels correlated with a worse outcome. Systolic blood pressure was significantly higher in ICH patients relative to rTPA-treated patients without haemorrhagic complications (p0.03). This study indicates that rTPA-induced haemorrhage is influenced by systolic blood pressure. More aggressive pharmacological reduction of hypertension during fibrinolysis and the subsequent 32h may reduce this complication.