Poster Presentations P3 P3-030
RATIO P-TAU/AB42 DISCRIMINATES ALZHEIMER’S DISEASE FROM SEMANTIC DEMENTIA AND FRONTOTEMPORAL DEMENTIA WITH HIGH SPECIFICITY
Leonardo C. De Souza1, Foudil Lamari2, Isabelle Le Ber1, Caroline Houillier1, He´le`ne Brasme1, Jose´ Luciano Monteiro Cunha1, Claude Jardel2, Bernard Hainque2, Bruno Dubois1, Marie Sarazin1, 1Centre des Maladies Cognitives et Comportementales, INSERM U610 Hosp. Pitie´-Salpeˆtrie`re, Paris, France; 2Service de Biochimie Me´tabolique Hop. Pitie´-Salpeˆtrie`re, Paris, France. Contact e-mail: leocruzsouza@hotmail. com Background: Cerebrospinal fluid (CSF) concentrations of tau, P-tau and amyloid beta 42 peptide (Ab42) have been studied in Alzheimer’s disease (AD). Few data are available concerning CSF levels of these biomarkers and their discriminating diagnostic value between AD and frontotemporal lobar degeneration (FTLD). Objective: To investigate the diagnostic value of CSF biomarkers to distinguish AD from FTD and SD. Methods: Ab42, total tau and tau phosphorylated at threonine 181 (p-tau181) were measured in CSF of 34 FTD, 8 SD and 42 AD. Only patients with a probable diagnosis according to the accepted clinical diagnostic criteria were included. The standard diagnostic examination protocol included medical history, neurological examination, neuropsychological testing, laboratory testing, brain imaging and a lumbar puncture. Results: CSF tau levels were higher in AD compared with both SD and FTD patients (p < 0.0001 for both). P-tau levels were also higher in AD compared with both SD and FTD (p < 0.0001 and p < 0.005, respectively). In the opposite, Ab42 was lower in AD compared with both FTD and SD patients (p < 0.005, for both). Ab42 (cut-off ¼ 379) alone had a specificity of 62.2% and a sensitivity of 83.6% in differentiating AD from FTDþSD, while the sensitivity of Tau (cut-off ¼ 446) and P-tau (cut-off ¼ 63.3) were 66% and 71.7% and the specificity 88.9% and 92.4%, respectively. The ratio P-Tau/Ab42 (cut-off ¼ 0.18) improved the diagnosis accuracy, when compared to the each biomarker considered separately. The ratio P-Tau/Ab42 differentiates AD patients from FTDþSD patients with a specificity of 88.9% and a sensitivity of 81.1%. The positive-predictive value (PPV) and the negative-predictive (NPV) referring for distinguishing separately AD from SD and FTD are given in the table: Conclusions: The validation studies of many drugs in development that are directed at changing AD pathogenesis require optimization of the specificity and sensitivity of existing criteria. CSF biomarkers may play a role in discriminating AD from FTD and SD, especially when the ratio P-Tau/Ab42 is employed.
PPV NPV
P3-031
AD vs FTD
AD vs SD
95% 85%
98% 85%
COMBINED CSF CYTOCHROME C LEVELS AND N200 LATENCY MAY PREDICT CONVERSION FROM MCI TO AD 1
2
2
Vasileios T. Papaliagkas , Magda N. Tsolaki , Vasileios K. Kimiskidis , Georgios Anogianakis1, 1Department of Experimental Physiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; 23rd Department of Neurology, G Papanikolaou Hospital, Thessaloniki, Greece. Contact e-mail:
[email protected] Background: Current evidence supports that, apoptosis, a fundamental neural procedure essential for the development and tissue homeostasis of multicellular organisms, is connected to AD pathogenesis. The aim of the present study was to investigate the role of cytochrome c-which plays an important role in the apoptosis mechanism-on the progress of Mild cognitive impairment (MCI) to Alzheimer’s Disease (AD). Methods: Fifty one patients diagnosed with MCI and 14 healthy individuals underwent lumbar puncture at baseline and their CSF cytochrome c levels were determined. A follow-up examination of cytochrome c levels took place in 20 patients after 11 months. During this period 5 of the patients developed AD. Auditory event-related potentials (AERPs) were also used in all patients both at baseline and fol-
P349
low-up to check if the progress of MCI is reflected to the values of the major AERP components. Results: MCI patients had significantly higher cytochrome c levels compared to control subjects (Mann-Whitney test, Z¼2.110, p¼0.018). MCI patients that later developed AD, had a higher increase over time in cytochrome c levels (Mann-Whitney test, p¼0.002, r¼0.63) and significantly prolonged N200 latency at baseline (Mann-Whitney test, p
