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Cerebrospinal Fluid Dehydroepiandrosterone Levels Are Correlated with Brain Dehydroepiandrosterone Levels, Elevated in Alzheimer’s Disease, and Related to Neuropathological Disease Stage

Durham Veterans Affairs Medical Center (J.C.N., L.J.S., V.M.P., M.W.M., J.D.K., J.L.S., P.S.C., R.P.C., R.D.M., C.E.M.), Durham, North Carolina 27705; Departments of Psychiatry and Behavioral Sciences (J.C.N., D.C.S., L.J.S., V.M.P., J.D.K., J.L.S., P.S.C., R.P.C., D.G.B., C.E.M.) and Surgery (R.D.M.) and Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (C.M.H., J.F.E.), Duke University Medical Center, Durham, North Carolina 27710; and Department of Psychiatry (J.A.L.), Columbia University College of Physicians and Surgeons, New York, New York 10032

Address all correspondence and requests for reprints to: Christine E. Marx, M.D., M.A., Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham Veterans Affairs Medical Center, 508 Fulton Street, MHSL 116A, Durham, North Carolina 27705. E-mail: marx0001{at}mc.duke.edu.

Objective: It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer’s disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex.

Design: DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer’s Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses.

Results: CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects.

Conclusions: These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.