BBB disruption, this study could lay the foundation for a controlled study including permeability measure- ments to clarify the value of BBB disruption in CNS lymphomas. 13 Because blood flow also is quite high compared with other primary and secondary brain tumors, although not influencing the overall extraction of water-soluble compounds from the plasma space into the extracellu- lar space, primary CNS lymphomas may also be ideal targets for treatment with lipophilic drugs such as te- mozolomide. 14 Our data show that primary CNS lymphomas are a different physiological entity compared with other brain tumors and render a basis for the development of rational treatment schedules using the unique physiol- ogy of these tumors. It also allows quantifying treat- ment effects especially those of glucosteroids on these tumors in a reproducible fashion. In conjunction with measurements of methotrexate levels, deriving an area- under-the-curve extraction fraction calculation for methotrexate can be performed and intratumoral drug concentrations can be estimated. References 1. Batchelor T, Carson K, O’Neill A, et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol 2003;21:1044 –1049. 2. Hoang-Xuan K, Taillandier L, Chinot O, et al. Chemotherapy alone as initial treatment for primary CNS lymphoma in pa- tients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol 2003;21: 2726 –2731. 3. Coulon A, Lafitte F, Hoang-Xuan K, et al. Radiographic find- ings in 37 cases of primary CNS lymphoma in immunocom- petent patients. Eur Radiol 2002;12:329 –340. 4. Zimmerman RA. Central nervous system lymphoma. Radiol Clin North Am 1990;28:697–721. 5. 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Brooks, MBBS, MPH, 1 John B. Kwok, PhD, 2 Cindy Kersaitis, BSc, 3 Gillian Gregory, BTech(Hons), 1 Claire E. Shepherd, PhD, 1 Farid Rahimi, PhD, 1 Peter R. Schofield, DSc, 2 and Jillian J. Kril, PhD 3 Presenilin-1 (PS-1) mutations can cause Pick’s disease without evidence of Alzheimer’s disease (AD). We de- scribe a family with a PS-1 M146L mutation and both Pick bodies and AD. Sarkosyl-insoluble hyperphosphory- lated tau showed three bands consistent with AD, al- though dephosphorylation showed primarily three-repeat isoforms. M146L mutant PS-1 may predispose to both Pick’s disease and AD by affecting multiple intracellular pathways involving tau phosphorylation and amyloid me- tabolism. Ann Neurol 2005;57:139 –143 Presenilin-1 (PS-1) mutations account for most familial Alzheimer’s disease (AD) and have been reported in fa- milial frontotemporal dementia (FTD), although most reports lack pathological confirmation. Dermaut and From the 1 Prince of Wales Medical Research Institute and the Uni- versity of New South Wales; 2 Garvan Institute of Medical Research and the University of New South Wales; 3 Centre for Education and Research on Ageing, The University of Sydney, Sydney, Australia. Received Aug 2, 2004, and in revised form Oct 12. Accepted for publication Oct 13, 2004. Published online Dec 27, 2004, in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ana.20366 Address correspondence to Dr Halliday, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney 2031, NSW, Australia. E-mail: g.halliday@unsw.edu.au © 2004 American Neurological Association 139 Published by Wiley-Liss, Inc., through Wiley Subscription Services