Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints.

TitleHypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints.
Publication TypeJournal Article
Year of Publication2008
AuthorsMosconi L, de Santi S, Brys M, Tsui WH, Pirraglia E, Glodzik-Sobanska L, Rich KE, Switalski R, Mehta PD, Pratico D, Zinkowski R, Blennow K, de Leon MJ
JournalBiol Psychiatry
Volume63
Issue6
Pagination609-18
Date Published2008 Mar 15
ISSN1873-2402
KeywordsAged, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Blood Glucose, Brain, Energy Metabolism, Female, Fluorodeoxyglucose F18, Genetic Carrier Screening, Humans, Male, Memory Disorders, Middle Aged, Peptide Fragments, Positron-Emission Tomography, Reference Values, tau Proteins
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 < or = .05). The combination of CSF and CMRglc measures significantly improved the accuracy of either measures alone in discriminating ApoE groups (86% accuracy, odds ratio [OR] = 4.1, p < .001) and E4+/SMC+ from all other subgroups (86% accuracy, OR = 3.7, p = .005). Parahippocampal gyrus CMRglc was the most accurate discriminator of SMC groups (75% accuracy, OR = 2.4, p < .001).

CONCLUSIONS: Normal E4 carriers with SMC show altered AD-related CSF and FDG-PET measures. Longitudinal studies are needed to assess whether these brain abnormalities foreshadow clinical decline.

DOI10.1016/j.biopsych.2007.05.030
Alternate JournalBiol Psychiatry
PubMed ID17720148
PubMed Central IDPMC2386268
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
MO1RR0096 / RR / NCRR NIH HHS / United States
R01 AG022374-01A1 / AG / NIA NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R01 AG012101 / AG / NIA NIH HHS / United States
R01 AG013616-16 / AG / NIA NIH HHS / United States
AG022374 / AG / NIA NIH HHS / United States
R01 AG012101-15 / AG / NIA NIH HHS / United States
AG13616 / AG / NIA NIH HHS / United States
P30 AG008051-10 / AG / NIA NIH HHS / United States
M01 RR000096-44 / RR / NCRR NIH HHS / United States
AG08051 / AG / NIA NIH HHS / United States
AG12101 / AG / NIA NIH HHS / United States
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
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