Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism

Alzheimer's Research and Therapy

Volumn 9, Issue 1, 2017, Pages 1-10

  Nielsen, Henrietta M ^a,b   Chen, Kewei ^c,d,e   Lee, Wendy ^c,e   Chen, Yinghua ^c,e   Bauer, Robert J ^c,d,e   Reiman, Eric ^c,e,f,g   Caselli, Richard ^e,h   Bu, Guojun ^a  

^a MAYO CLINIC   (United States)

^b STOCKHOLM UNIVERSITY   (Sweden)

^c BANNER ALZHEIMER S INSTITUTE   (United States)

^d ARIZONA STATE UNIVERSITY   (United States)

^e ARIZONA ALZHEIMER S CONSORTIUM   (United States)

^f UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^g TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

^h MAYO CLINIC   (United States)

Author keywords

Apolipoprotein E; Cognition; Dementia; Gray matter volume; Plasma

Indexed keywords

APOLIPOPROTEIN E; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; ISOPROTEIN; GLUCOSE;

ADULT; ANTERIOR CINGULATE; ARTICLE; BRAIN METABOLISM; BRAIN SIZE; COGNITION; CONTROLLED STUDY; FEMALE; FRONTAL LOBE; GENETIC PREDISPOSITION; GLUCOSE METABOLISM; GRAY MATTER; HETEROZYGOTE; HIPPOCAMPUS; HUMAN; MAJOR CLINICAL STUDY; MALE; MASS SPECTROMETRY; NEUROPSYCHOLOGICAL TEST; NUCLEAR MAGNETIC RESONANCE IMAGING; OCCIPITAL LOBE; POSITRON EMISSION TOMOGRAPHY; TEMPORAL LOBE; AGE; AGED; BLOOD; BRAIN; COHORT ANALYSIS; DIAGNOSTIC IMAGING; GENETICS; METABOLISM; MIDDLE AGED; ORGAN SIZE; SEX DIFFERENCE;

AGE FACTORS; AGED; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; BRAIN; COGNITION; COHORT STUDIES; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GLUCOSE; GRAY MATTER; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; MASS SPECTROMETRY; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; ORGAN SIZE; POSITRON-EMISSION TOMOGRAPHY; SEX FACTORS;

EID: 85010911819     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/s13195-016-0231-9     Document Type: Article

References (53)

1. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261:921-3.
2. Berge G, Sando SB, Rongve A, Aarsland D, White LR. Apolipoprotein E epsilon2 genotype delays onset of dementia with Lewy bodies in a Norwegian cohort. J Neurol Neurosurg Psychiatry. 2014;85:1227-31. doi:10.1136/jnnp-2013-307228.
3. Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell Jr PC, Rimmler JB, Locke PA, Conneally PM, Schmader KE, et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. 1994;7:180-4.
4. Kok E, Haikonen S, Luoto T, Huhtala H, Goebeler S, Haapasalo H, Karhunen PJ. Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Ann Neurol. 2009;65:650-7.
5. Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, Mintun MA. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010;67:122-31. doi:10.1002/ana.21843.
6. Altmann A, Tian L, Henderson VW, Greicius MD. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014;75:563-73. doi:10.1002/ana.24135.
7. Rocca WA, Mielke MM, Vemuri P, Miller VM. Sex and gender differences in the causes of dementia: a narrative review. Maturitas. 2014. doi:10.1016/j.maturitas.2014.05.008.
8. Tai LM, Mehra S, Shete V, Estus S, Rebeck GW, Bu G, LaDu MJ. Soluble apoE/Abeta complex: mechanism and therapeutic target for APOE4-induced AD risk. Mol Neurodegener. 2014;9:2. doi:10.1186/1750-1326-9-2.
9. Reiman EM, Caselli RJ, Chen K, Alexander GE, Bandy D, Frost J. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc Natl Acad Sci U S A. 2001;98:3334-9. doi:10.1073/pnas.061509598.
10. Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996;334:752-8. doi:10.1056/NEJM199603213341202.
11. Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci U S A. 2005;102:8299-302. doi:10.1073/pnas.0500579102.
12. Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000;97:6037-42. doi:10.1073/pnas.090106797.
13. Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A, Adamson CF, Chang L, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995;273:942-7.
14. O'Dwyer L, Lamberton F, Matura S, Tanner C, Scheibe M, Miller J, Rujescu D, Prvulovic D, Hampel H. Reduced hippocampal volume in healthy young ApoE4 carriers: an MRI study. PLoS One. 2012;7, e48895. doi:10.1371/journal.pone.0048895.
15. Honea RA, Vidoni E, Harsha A, Burns JM. Impact of APOE on the healthy aging brain: a voxel-based MRI and DTI study. J Alzheimers Dis. 2009;18:553-64. doi:10.3233/JAD-2009-1163.
16. Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2004;101:284-9. doi:10.1073/pnas.2635903100.
17. Dean 3rd DC, Jerskey BA, Chen K, Protas H, Thiyyagura P, Roontiva A, O'Muircheartaigh J, Dirks H, Waskiewicz N, Lehman K, et al. Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study. JAMA Neurol. 2014;71:11-22. doi:10.1001/jamaneurol.2013.4544.
18. Arnaiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, Valind S, Nordberg A. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport. 2001;12:851-5.
19. Chetelat G, Desgranges B, de la Sayette V, Viader F, Eustache F, Baron JC. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer's disease? Neurology. 2003;60:1374-7.
20. Lin LY, Zhang J, Dai XM, Xiao NA, Wu XL, Wei Z, Fang WT, Zhu YG, Chen XC. Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice. Mol Neurodegener. 2016;11:51. doi:10.1186/s13024-016-0107-2.
21. Verghese PB, Castellano JM, Holtzman DM. Apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurol. 2011;10:241-52. doi:10.1016/S1474-4422(10)70325-2.
22. Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9:106-18. doi:10.1038/nrneurol.2012.263.
23. Mulder SD, Nielsen HM, Blankenstein MA, Eikelenboom P, Veerhuis R. Apolipoproteins E and J interfere with amyloid-beta uptake by primary human astrocytes and microglia in vitro. Glia. 2014;62:493-503. doi:10.1002/glia.22619.
24. Nielsen HM, Mulder SD, Musters RJP, Beliën JAM, Eikelenboom P, Veerhuis R. Astrocytic Abeta1-42 uptake is determined by Abeta-aggregation state and the presence of amyloid-associated proteins. Glia. 2010;58:1235-46.
25. Verghese PB, Castellano JM, Garai K, Wang Y, Jiang H, Shah A, Bu G, Frieden C, Holtzman DM. ApoE influences amyloid-beta (Abeta) clearance despite minimal apoE/Abeta association in physiological conditions. Proc Natl Acad Sci U S A. 2013;110:E1807-16. doi:10.1073/pnas.1220484110.
26. Fu Y, Zhao J, Atagi Y, Nielsen HM, Liu CC, Zheng H, Shinohara M, Kanekiyo T, Bu G. Apolipoprotein E lipoprotein particles inhibit amyloid-beta uptake through cell surface heparan sulphate proteoglycan. Mol Neurodegener. 2016;11:37. doi:10.1186/s13024-016-0099-y.
27. Riddell DR, Zhou H, Atchison K, Warwick HK, Atkinson PJ, Jefferson J, Xu L, Aschmies S, Kirksey Y, Hu Y, et al. Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J Neurosci. 2008;28:11445-53.
28. Cruchaga C, Kauwe JS, Nowotny P, Bales K, Pickering EH, Mayo K, Bertelsen S, Hinrichs A, Fagan AM, Holtzman DM, et al. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease. Hum Mol Genet. 2012;21:4558-71. doi:10.1093/hmg/dds296.
29. Darreh-Shori T, Modiri N, Blennow K, Baza S, Kamil C, Ahmed H, Andreasen N, Nordberg A. The apolipoprotein E epsilon4 allele plays pathological roles in AD through high protein expression and interaction with butyrylcholinesterase. Neurobiol Aging. 2011;32:1236-48. doi:10.1016/j.neurobiolaging.2009.07.015.
30. Wahrle SE, Shah AR, Fagan AM, Smemo S, Kauwe JS, Grupe A, Hinrichs A, Mayo K, Jiang H, Thal LJ, et al. Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms. Mol Neurodegener. 2007;2:7. doi:10.1186/1750-1326-2-7.
31. Wildsmith KR, Basak JM, Patterson BW, Pyatkivskyy Y, Kim J, Yarasheski KE, Wang JX, Mawuenyega KG, Jiang H, Parsadanian M, et al. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS. PLoS One. 2012;7, e38013. doi:10.1371/journal.pone.0038013.
32. Martinez-Morillo E, Nielsen HM, Batruch I, Drabovich AP, Begcevic I, Lopez MF, Minthon L, Bu G, Mattsson N, Portelius E, et al. Assessment of peptide chemical modifications on the development of an accurate and precise multiplex selected reaction monitoring assay for apolipoprotein e isoforms. J Proteome Res. 2014;13:1077-87. doi:10.1021/pr401060x.
33. Martinez-Morillo E, Hansson O, Atagi Y, Bu G, Minthon L, Diamandis EP, Nielsen HM. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. Acta Neuropathol. 2014;127:633-43. doi:10.1007/s00401-014-1266-2.
34. Rasmussen KL, Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Plasma levels of apolipoprotein E and risk of dementia in the general population. Ann Neurol. 2015;77:301-11. doi:10.1002/ana.24326.
35. Caselli RJ, Dueck AC, Locke DE, Hoffman-Snyder CR, Woodruff BK, Rapcsak SZ, Reiman EM. Longitudinal modeling of frontal cognition in APOE epsilon4 homozygotes, heterozygotes, and noncarriers. Neurology. 2011;76:1383-8. doi:10.1212/WNL.0b013e3182167147.
36. Caselli RJ, Dueck AC, Osborne D, Sabbagh MN, Connor DJ, Ahern GL, Baxter LC, Rapcsak SZ, Shi J, Woodruff BK, et al. Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. N Engl J Med. 2009;361:255-63. doi:10.1056/NEJMoa0809437.
37. Caselli RJ, Locke DE, Dueck AC, Knopman DS, Woodruff BK, Hoffman-Snyder C, Rademakers R, Fleisher AS, Reiman EM. The neuropsychology of normal aging and preclinical Alzheimer's disease. Alzheimers Dement. 2014;10:84-92. doi:10.1016/j.jalz.2013.01.004.
38. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:270-9. doi:10.1016/j.jalz.2011.03.008.
39. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:263-9. doi:10.1016/j.jalz.2011.03.005.
40. Reiman EM, Uecker A, Caselli RJ, Lewis S, Bandy D, de Leon MJ, De Santi S, Convit A, Osborne D, Weaver A, et al. Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Ann Neurol. 1998;44:288-91. doi:10.1002/ana.410440226.
41. Talairach J, Tournoux P. Co-planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System - an Approach to Cerebral Imaging. Stuttgart: Thieme Medical Publishers; 1988.
42. Reiman EM, Lane RD, Ahern GL, Schwartz GE, Davidson RJ, Friston KJ, Yun LS, Chen K. Neuroanatomical correlates of externally and internally generated human emotion. Am J Psychiatry. 1997;154:918-25. doi:10.1176/ajp.154.7.918.
43. Reiman EM, Chen K, Langbaum JB, Lee W, Reschke C, Bandy D, Alexander GE, Caselli RJ. Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer's disease and normal aging. Neuroimage. 2010;49:169-76. doi:10.1016/j.neuroimage.2009.07.025.
44. Song F, Poljak A, Crawford J, Kochan NA, Wen W, Cameron B, Lux O, Brodaty H, Mather K, Smythe GA, et al. Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals. PLoS One. 2012;7, e34078. doi:10.1371/journal.pone.0034078.
45. Teng E, Chow N, Hwang KS, Thompson PM, Gylys KH, Cole GM, Jack Jr CR, Shaw LM, Trojanowski JQ, Soares HD, et al. Low plasma ApoE levels are associated with smaller hippocampal size in the Alzheimer's disease neuroimaging initiative cohort. Dement Geriatr Cogn Disord. 2015;39:154-66. doi:10.1159/000368982.
46. Ewers M, Brendel M, Rizk-Jackson A, Rominger A, Bartenstein P, Schuff N, Weiner MW, Alzheimer's Disease Neuroimaging I. Reduced FDG-PET brain metabolism and executive function predict clinical progression in elderly healthy subjects. NeuroImage Clin. 2014;4:45-52. doi:10.1016/j.nicl.2013.10.018.
47. Lowe VJ, Weigand SD, Senjem ML, Vemuri P, Jordan L, Kantarci K, Boeve B, Jack Jr CR, Knopman D, Petersen RC. Association of hypometabolism and amyloid levels in aging, normal subjects. Neurology. 2014;82:1959-67. doi:10.1212/WNL.0000000000000467.
48. Kraft HG, Menzel HJ, Hoppichler F, Vogel W, Utermann G. Changes of genetic apolipoprotein phenotypes caused by liver-transplantation - implications for apolipoprotein synthesis. J Clin Investig. 1989;83:137-42.
49. Riedel BC, Thompson PM, Brinton RD. Age, APOE and sex: triad of risk of Alzheimer's disease. J Steroid Biochem Mol Biol. 2016;160:134-47.
50. Bu G. Apolipoprotein E, and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat Rev Neurosci. 2009;10:333-44. doi:10.1038/nrn2620.
51. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349-56.
52. Payami H, Zareparsi S, Montee KR, Sexton GJ, Kaye JA, Bird TD, Yu CE, Wijsman EM, Heston LL, Litt M, et al. Gender difference in Apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. Am J Hum Genet. 1996;58:803-11.
53. Alexander GE, Chen K, Pietrini P, Rapoport SI, Reiman EM. Longitudinal PET Evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer's disease treatment studies. Am J Psychiatry. 2002;159:738-45. doi:10.1176/appi.ajp.159.5.738.