Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints.
| Publication Type | Academic Article |
| Authors | Mosconi L, De Santi S, Brys M, Tsui W, Pirraglia E, Glodzik-Sobanska L, Rich K, Switalski R, Mehta P, Pratico D, Zinkowski R, Blennow K, de Leon M |
| Journal | Biol Psychiatry |
| Volume | 63 |
| Issue | 6 |
| Pagination | 609-18 |
| Date Published | 08/27/2007 |
| ISSN | 1873-2402 |
| Keywords | Alzheimer Disease, Apolipoprotein E4, Biomarkers, Blood Glucose, Energy Metabolism, Genetic Carrier Screening, Memory Disorders, Positron-Emission Tomography |
| 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. |
| DOI | 10.1016/j.biopsych.2007.05.030 |
| PubMed ID | 17720148 |
| PubMed Central ID | PMC2386268 |