Apolipoproteins E and C1 and Brain Morphology in Memory Impaired Elders

Overview

Journal Neurogenetics

Specialty Neurology

Date 2003 May 9

PMID 12736801

Citations 15

Authors

J M Serra-Grabulosa

P Salgado-Pineda

C Junque

C Sole-Padulles

P Moral

A Lopez-Alomar

T Lopez

A Lopez-Guillen

N Bargallo

J M Mercader

I C Clemente

D Bartres-Faz

Affiliations

Soon will be listed here.

Abstract

Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

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References

Wenham P, Price W, Blandell G . Apolipoprotein E genotyping by one-stage PCR. Lancet. 1991; 337(8750):1158-9. DOI: 10.1016/0140-6736(91)92823-k. View

Xu Y, Berglund L, Ramakrishnan R, Mayeux R, Ngai C, Holleran S . A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E. J Lipid Res. 1998; 40(1):50-8. View

Jack Jr C, Twomey C, Zinsmeister A, Sharbrough F, Petersen R, Cascino G . Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. Radiology. 1989; 172(2):549-54. DOI: 10.1148/radiology.172.2.2748838. View

Strittmatter W, Saunders A, Schmechel D, Pericak-Vance M, Enghild J, Salvesen G . Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993; 90(5):1977-81. PMC: 46003. DOI: 10.1073/pnas.90.5.1977. View

Nillesen W, Smeets H, van Oost B . Human ApoCI HpaI restriction site polymorphism revealed by the polymerase chain reaction. Nucleic Acids Res. 1990; 18(11):3428. PMC: 330980. DOI: 10.1093/nar/18.11.3428-a. View

Jong M, van Dijk K, Dahlmans V, van der Boom H, Kobayashi K, Oka K . Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very-low-density-lipoprotein receptor. Biochem J. 1999; 338 ( Pt 2):281-7. PMC: 1220053. View

Jack Jr C, Petersen R, Xu Y, OBrien P, Smith G, Ivnik R . Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology. 1999; 52(7):1397-403. PMC: 2730146. DOI: 10.1212/wnl.52.7.1397. View

Squire L . The medial temporal lobe memory system. Science. 1991; 253(5026):1380-6. DOI: 10.1126/science.1896849. View

Tysoe C, GALINSKY D, Robinson D, Brayne C, Huppert F, Dening T . Apo E and Apo CI loci are associated with dementia in younger but not older late-onset cases. Dement Geriatr Cogn Disord. 1998; 9(4):191-8. DOI: 10.1159/000017046. View

10.

Scacchi R, Gambina G, Ruggeri M, Martini M, Ferrari G, Silvestri M . Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease. Neurosci Lett. 1999; 259(1):33-6. DOI: 10.1016/s0304-3940(98)00889-1. View

11.

Bartres-Faz D, Clemente I, Junque C, Valveny N, Lopez-Alomar A, Lopez-Guillen A . APOE and APOC1 genetic polymorphisms in age-associated memory impairment. Neurogenetics. 2001; 3(4):215-9. DOI: 10.1007/s100480100122. View

12.

Soininen H, Partanen K, Pitkanen A, Vainio P, Hanninen T, Hallikainen M . Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment: correlation to visual and verbal memory. Neurology. 1994; 44(9):1660-8. DOI: 10.1212/wnl.44.9.1660. View

13.

Chartier-Harlin M, Parfitt M, Legrain S, Perez-Tur J, Brousseau T, Evans A . Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Hum Mol Genet. 1994; 3(4):569-74. DOI: 10.1093/hmg/3.4.569. View

14.

GOLDMAN W, Morris J . Evidence that age-associated memory impairment is not a normal variant of aging. Alzheimer Dis Assoc Disord. 2001; 15(2):72-9. DOI: 10.1097/00002093-200104000-00006. View

15.

Bigler E, Lowry C, Anderson C, Johnson S, Terry J, Steed M . Dementia, quantitative neuroimaging, and apolipoprotein E genotype. AJNR Am J Neuroradiol. 2000; 21(10):1857-68. PMC: 7974277. View

16.

Free S, Bergin P, Fish D, Cook M, Shorvon S, Stevens J . Methods for normalization of hippocampal volumes measured with MR. AJNR Am J Neuroradiol. 1995; 16(4):637-43. PMC: 8332287. View

17.

Petit-Turcotte C, Stohl S, Beffert U, Cohn J, Aumont N, Tremblay M . Apolipoprotein C-I expression in the brain in Alzheimer's disease. Neurobiol Dis. 2001; 8(6):953-63. DOI: 10.1006/nbdi.2001.0441. View

18.

Hashimoto M, Yasuda M, Tanimukai S, Matsui M, Hirono N, Kazui H . Apolipoprotein E epsilon 4 and the pattern of regional brain atrophy in Alzheimer's disease. Neurology. 2001; 57(8):1461-6. DOI: 10.1212/wnl.57.8.1461. View

19.

Petersen R, Smith G, Waring S, Ivnik R, Tangalos E, Kokmen E . Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999; 56(3):303-8. DOI: 10.1001/archneur.56.3.303. View

20.

Bartres-Faz D, Junque C, Clemente I, Serra-Grabulosa J, Guardia J, Lopez-Alomar A . MRI and genetic correlates of cognitive function in elders with memory impairment. Neurobiol Aging. 2001; 22(3):449-59. DOI: 10.1016/s0197-4580(01)00207-x. View