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

• Published in: Biological psychiatry (1969) Vol. 63; no. 6; pp. 609 - 618
• Main Authors: Mosconi, Lisa, De Santi, Susan, Brys, Miroslaw, Tsui, Wai H, Pirraglia, Elizabeth, Glodzik-Sobanska, Lidia, Rich, Kenneth E, Switalski, Remigius, Mehta, Pankaj D, Pratico, Domenico, Zinkowski, Ray, Blennow, Kay, de Leon, Mony J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.03.2008; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - genetics; Alzheimer’s disease; amyloid beta; Amyloid beta-Peptides - cerebrospinal fluid; ApoE; Apolipoprotein E4 - genetics; Biological and medical sciences; Biomarkers - cerebrospinal fluid; Blood Glucose - metabolism; Brain - diagnostic imaging; Brain - metabolism; CSF; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Energy Metabolism - genetics; FDG-PET; Female; Fluorodeoxyglucose F18; Genetic Carrier Screening; Humans; isoprostane; Male; Medical sciences; Memory Disorders - cerebrospinal fluid; Memory Disorders - genetics; Middle Aged; Neurology; Neurosciences; Neurovetenskaper; normal aging; Organic mental disorders. Neuropsychology; Peptide Fragments - cerebrospinal fluid; Positron-Emission Tomography; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reference Values; subjective memory complaints; tau; tau Proteins - cerebrospinal fluid; FDG-PET; subjective memory complaints; Alzheimer’s disease; CSF; normal aging; tau; ApoE; isoprostane; amyloid beta; Radionuclide study; Memory disorder; Senescence; Cognitive disorder; Self evaluation; Alzheimer disease; Cerebrospinal fluid; Apolipoprotein E; Degenerative disease; Memory complaint; Alzheimer's disease; Nervous system diseases; Cerebral disorder; Tau protein; β Amyloid protein; Central nervous system disease; Positron emission tomography; Emission tomography
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2007.05.030

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 tau231 (P-Tau), 40 and 42 amino acid forms of β-amyloid (Aβ40 and Aβ42), and F2 -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/Aβ42 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/Aβ42 levels as compared with all other subgroups ( p ’s ≤ .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.