118 Traumatic Brain Injury Elevates the Alzheimer’s Amyloid Peptide A> 42 in Human CSF A Possible Role for Nerve Cell Injury M.R. EMMERLING, a,e M.C. MORGANTI-KOSSMANN, b T. KOSSMANN, b P.F. STAHEL, b M.D. WATSON, a L.M. EVANS, a P.D. MEHTA, c K. SPIEGEL, a Y.-M. KUO, d A.E. ROHER, d AND C.A. RABY a a Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road., Ann Arbor, Michigan 48105, USA b Department of Surgery, Division of Trauma Surgery, University Hospital, CH-8091 Zürich, Switzerland c New York Institute for Basic Research, 1050 Forrest Hill Road, Staten Island, New York 10314, USA d Haldeman Laboratory for Alzheimer’s Disease Research, Sun Health Research Institute, Sun City, Arizona 85372, USA ABSTRACT: The increased risk for Alzheimer’s Disease (AD) associated with traumatic brain injury (TBI) suggests that environmental insults may influ- ence the development of this age-related dementia. Recently, we have shown that the levels of the >-amyloid peptide (A> 1–42 ) increase in the cerebrospinal fluid (CSF) of patients after severe brain injury and remain elevated for some time after the initial event. The relationships of elevated A> with markers of blood-brain barrier (BBB) disruption, inflammation, and nerve cell or axonal injury were evaluated in CSF samples taken daily from TBI patients. This analysis reveals that the rise in A> 1–42 is best correlated with possible markers of neuronal or axonal injury, the cytoskeletal protein tau, neuron-specific eno- lase (NSE), and apolipoprotein E (ApoE). Similar or better correlations were observed between A> 1–40 and the three aforementioned markers. These results imply that the degree of brain injury may play a decisive role in determining the levels of A> 1–42 and A> 1–40 in the CSF of TBI patients. Inflammation and alterations in BBB may play lesser, but nonetheless significant, roles in deter- mining the A> level in CSF after brain injury. INTRODUCTION How does the β-amyloid peptide (Aβ) come to dominate the Alzheimer disease (AD) brain? In a handful of AD cases (less than 5%), genetic mutations in the genes coding for the β-amyloid precursor protein (AβPP) on chromosome 21, or for pres- e Address for correspondence: Mark R. Emmerling, Ph.D., Parke-Davis, 2800 Plymouth Road, Ann Arbor, MI 48106. Tel.: (734) 622-5917; fax: (734) 622-1193. e-mail: mark.emmerling@wl.com