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Hypometabolism and Altered Cerebrospinal Fluid Markers in Normal Apolipoprotein E E4 Carriers with Subjective Memory Complaints

Journal article
Authors L. Mosconi
S. De Santi
M. Brys
W. H. Tsui
E. Pirraglia
L. Glodzik-Sobanska
K. E. Rich
R. Switalski
P. D. Mehta
D. Pratico
R. Zinkowski
Kaj Blennow
M. J. de Leon
Published in Biological Psychiatry
Volume 63
Issue 6
Pages 609-618
ISSN 0006-3223
Publication year 2007
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 609-618
Language en
Links dx.doi.org/10.1016/j.biopsych.2007....
Subject categories Neurochemistry

Abstract

BACKGROUND: We examined whether cerebral metabolic rates for glucose (CMRglc) on 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) are altered in cognitively normal apolipoprotein E (ApoE) E4 carriers with subjective memory complaints (SMC). METHODS: Twenty-eight middle-aged normal subjects (NL) were examined, including 13 E4 carriers (E4+; 6 with SMC [SMC+] and 7 without SMC [SMC-]) and 15 noncarriers (E4-; 7 SMC+ and 8 SMC-). Subjects received an FDG-PET scan and a lumbar puncture to measure CSF total (T-Tau) and hyperphosphorylated tau(231) (P-Tau), 40 and 42 amino acid forms of beta-amyloid (Abeta40 and Abeta42), and F(2)-isoprostane (IP). RESULTS: As compared with E4-, E4+ subjects showed decreased CMRglc in AD-related brain regions and associated higher CSF IP, P-Tau, T-Tau, and P-Tau/Abeta42 levels (p's < .05). As compared with SMC-, SMC+ subjects showed reduced parietotemporal and parahippocampal gyrus (PHG) CMRglc. A significant ApoE by SMC status interaction was found, with the E4+/SMC+ showing the lowest PHG CMRglc and the highest CSF IP, P-Tau, and P-Tau/Abeta42 levels as compared with all other subgroups (p's

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