title: Diet and age interactions with regards to cholesterol regulation and brain pathogenesis.
abstract: Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use) to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur and Consejo Nacional de Investigaciones Científicas y Técnicas, Bahía Blanca, Argentina.
authors.forename: Romina M
authors.initials: RM
authors.lastname: Uranga
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keller
references.citation: Mol Neurodegener. 2009 Oct 24;4:42
references.pmid: 19852847
references.citation: Endocr Rev. 1993 Feb;14(1):20-39
references.pmid: 8491152
references.citation: Life Sci. 2005 Sep 30;77(20):2552-73
references.pmid: 15936776
references.citation: Am J Clin Nutr. 2002 Aug;76(2):326-30
references.pmid: 12145002
references.citation: Neuron. 2009 Aug 13;63(3):287-303
references.pmid: 19679070
references.citation: Vascul Pharmacol. 2002 Jun;38(6):323-37
references.pmid: 12529927
references.citation: Curr Opin Plant Biol. 2002 Oct;5(5):388-95
references.pmid: 12183176
references.citation: Neurology. 2001 Jun 26;56(12):1683-9
references.pmid: 11425934
references.citation: J Am Coll Cardiol. 2000 Feb;35(2):265-70
references.pmid: 10676668
references.citation: Nature. 1970 Jan 31;225(5231):464-7
references.pmid: 5440881
references.citation: Neurosci Lett. 1998 Jun 19;249(2-3):71-4
references.pmid: 9682819
references.citation: Ann Neurol. 2000 Jun;47(6):739-47
references.pmid: 10852539
references.citation: Neurobiol Aging. 2000 Mar-Apr;21(2):161-9
references.pmid: 10867201
references.citation: Neurobiol Aging. 2000 May-Jun;21(3):383-421
references.pmid: 10858586
references.citation: Neurobiol Aging. 2000 Mar-Apr;21(2):207-14
references.pmid: 10867205
references.citation: Exp Neurol. 2006 Aug;200(2):460-7
references.pmid: 16696972
references.citation: J Neurosci. 2007 Jun 13;27(24):6417-27
references.pmid: 17567802
references.citation: Science. 2001 Nov 9;294(5545):1354-7
references.pmid: 11701931
references.citation: Mov Disord. 1998;13 Suppl 1:13-6
references.pmid: 9613713
references.citation: Biofactors. 2008;33(3):225-36
references.pmid: 19478426
references.citation: J Clin Invest. 1985 Oct;76(4):1501-13
references.pmid: 3932467
references.citation: Am J Clin Nutr. 1962 May;10:403-9
references.pmid: 14472560
references.citation: J Lipid Res. 2002 Nov;43(11):1950-9
references.pmid: 12401894
references.citation: Am J Med. 1987 Jan 26;82(1B):1-8
references.pmid: 3544829
references.citation: J Biol Chem. 2004 Sep 24;279(39):40987-93
references.pmid: 15269217
references.citation: JAMA. 1997 Mar 12;277(10):813-7
references.pmid: 9052711
references.citation: Arterioscler Thromb Vasc Biol. 1997 Aug;17(8):1521-6
references.pmid: 9301630
references.citation: Biochemistry. 2001 Feb 27;40(8):2548-54
references.pmid: 11327877
references.citation: Biochim Biophys Acta. 1987 Jan 13;917(1):148-61
references.pmid: 3539206
references.citation: Tohoku J Exp Med. 2004 Jul;203(3):145-54
references.pmid: 15240923
references.citation: J Alzheimers Dis. 2001 Apr;3(2):221-229
references.pmid: 12214063
references.citation: Gastroenterology. 2005 Aug;129(2):718-34
references.pmid: 16083725
references.citation: J Gerontol A Biol Sci Med Sci. 2002 Jul;57(7):M414-8
references.pmid: 12084801
references.citation: J Clin Invest. 1973 Oct;52(10):2389-97
references.pmid: 4729038
references.citation: Neurology. 2009 Mar 3;72(9):829-34
references.pmid: 19255410
references.citation: Neuron. 2007 Oct 4;56(1):66-78
references.pmid: 17920016
references.citation: Ageing Res Rev. 2009 Oct;8(4):339-48
references.pmid: 19576300
references.citation: Acta Neurol Scand Suppl. 2006;185:43-9
references.pmid: 16866910
references.citation: Biochem Biophys Res Commun. 2006 Aug 18;347(1):192-9
references.pmid: 16814251
references.citation: Braz J Med Biol Res. 2006 Feb;39(2):189-94
references.pmid: 16470305
references.citation: J Biol Chem. 1997 Dec 5;272(49):30766-73
references.pmid: 9388216
references.citation: J Neurosci Res. 1998 Oct 1;54(1):58-67
references.pmid: 9778150
references.citation: J Lipid Res. 1998 Aug;39(8):1594-600
references.pmid: 9717719
references.citation: Dement Geriatr Cogn Disord. 2006;22(4):301-5
references.pmid: 16926537
references.citation: J Clin Invest. 1991 Jul;88(1):270-81
references.pmid: 2056122
references.citation: Stroke. 2003 Apr;34(4):875-80
references.pmid: 12649507
references.citation: Lancet. 2000 Nov 11;356(9242):1627-31
references.pmid: 11089820
references.citation: Stroke. 1999 Sep;30(9):1969-73
references.pmid: 10471452
references.citation: Neuron. 2001 Mar;29(3):571-81
references.pmid: 11301018
references.citation: Lancet Neurol. 2005 Dec;4(12):841-52
references.pmid: 16297842
references.citation: Endocrinology. 1980 Dec;107(6):1875-9
references.pmid: 7428695
references.citation: Neurobiol Dis. 2000 Aug;7(4):321-31
references.pmid: 10964604
references.citation: Biochem J. 1966 Dec;101(3):618-26
references.pmid: 16742434
references.citation: Eur J Neurosci. 2003 Jan;17(1):93-102
references.pmid: 12534972
references.citation: Neurology. 2005 Jun 28;64(12):2040-5
references.pmid: 15985568
references.citation: Neuroepidemiology. 2004 Jan-Apr;23(1-2):45-52
references.pmid: 14739567
references.citation: J Neurochem. 2006 Oct;99(2):438-49
references.pmid: 17029598
references.citation: N Engl J Med. 2000 Jan 27;342(4):240-5
references.pmid: 10648765
references.citation: Nat Med. 2002 Nov;8(11):1211-7
references.pmid: 12411947
references.citation: Brain Res. 1997 Mar 21;751(2):307-14
references.pmid: 9099820
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13909-14
references.pmid: 15365176
references.citation: Australas Ann Med. 1958 Nov;7(4):336-9
references.pmid: 13607334
references.citation: Nat Genet. 1997 Nov;17(3):263-4
references.pmid: 9354781
references.citation: Biochem J. 1984 Aug 15;222(1):1-15
references.pmid: 6383353
references.citation: Ann Neurol. 1995 Aug;38(2):254-9
references.pmid: 7654074
references.citation: Arch Biochem Biophys. 2000 Jun 15;378(2):259-68
references.pmid: 10860543
references.citation: Int J Epidemiol. 1999 Dec;28(6):1102-9
references.pmid: 10661654
references.citation: Curr Opin Lipidol. 1994 Jun;5(3):160-5
references.pmid: 7952909
references.citation: Neurosci Lett. 1994 Jul 18;176(1):45-6
references.pmid: 7970234
references.citation: J Neurochem. 1992 Nov;59(5):1646-53
references.pmid: 1402910
references.citation: Mol Cell Neurosci. 2010 Jan;43(1):33-42
references.pmid: 19660552
references.citation: Nutr Rev. 2002 Sep;60(9):289-93
references.pmid: 12296456
references.citation: Ann Neurol. 1998 Sep;44(3 Suppl 1):S45-52
references.pmid: 9749572
references.citation: Trends Plant Sci. 2002 Sep;7(9):405-10
references.pmid: 12234732
references.citation: J Pathol. 2007 Jan;211(2):181-7
references.pmid: 17200950
references.citation: Biochim Biophys Acta. 1973 Oct 5;320(3):681-6
references.pmid: 4356538
references.citation: Stroke. 2008 Feb;39(2):497-502
references.pmid: 18174491
references.citation: J Biol Chem. 2004 Sep 24;279(39):41197-207
references.pmid: 15269218
references.citation: J Biol Chem. 1987 Oct 15;262(29):14352-60
references.pmid: 3115992
references.citation: Novartis Found Symp. 2002;242:222-42; discussion 242-6
references.pmid: 11855690
references.citation: Life Sci. 2001 Feb 16;68(13):1495-503
references.pmid: 11253166
references.citation: J Clin Invest. 2002 Sep;110(5):597-603
references.pmid: 12208858
references.citation: Neurobiol Dis. 2002 Apr;9(3):305-18
references.pmid: 11950276
references.citation: Diabetes Care. 1981 Jul-Aug;4(4):493-501
references.pmid: 7049632
references.citation: Arterioscler Thromb Vasc Biol. 1997 Jun;17(6):1163-70
references.pmid: 9194769
references.citation: J Intern Med. 1997 Oct;242(4):329-37
references.pmid: 9366812
references.citation: Annu Rev Biochem. 2009;78:1017-40
references.pmid: 19489738
references.citation: Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1141-51
references.pmid: 16910762
references.citation: J Neurochem. 1998 May;70(5):2070-81
references.pmid: 9572293
references.citation: J Clin Invest. 1991 Feb;87(2):591-6
references.pmid: 1991842
references.citation: J Physiol. 2005 Feb 1;562(Pt 3):647-53
references.pmid: 15611017
references.citation: BMC Neurosci. 2007 Jan 02;8:1
references.pmid: 17199885
references.citation: Brain Res. 1997 Mar 28;752(1-2):189-96
references.pmid: 9106456
references.citation: J Neurosci. 2005 Mar 16;25(11):2803-10
references.pmid: 15772340
references.citation: Future Lipidol. 2008 Oct;3(5):505-530
references.pmid: 19649144
references.citation: Arterioscler Thromb Vasc Biol. 1995 Sep;15(9):1352-8
references.pmid: 7670949
references.citation: Am J Clin Nutr. 1986 Dec;44(6):805-15
references.pmid: 3788831
references.citation: Arterioscler Thromb Vasc Biol. 2004 May;24(5):806-15
references.pmid: 14764421
references.citation: J Neuroimmunol. 2002 Nov;132(1-2):99-112
references.pmid: 12417439
references.citation: J Neurosci. 2006 May 10;26(19):4985-94
references.pmid: 16687490
references.citation: J Biol Chem. 1996 Feb 23;271(8):4436-40
references.pmid: 8626795
references.citation: J Neurol. 2003 Oct;250 Suppl 3:III30-9
references.pmid: 14579122
references.citation: Gastroenterology. 1999 Jun;116(6):1413-9
references.pmid: 10348825
references.citation: Neurol Res. 2004 Jul;26(5):525-39
references.pmid: 15265270
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6460-4
references.pmid: 9600988
references.citation: Arterioscler Thromb Vasc Biol. 1998 May;18(5):738-46
references.pmid: 9598832
references.citation: Biochem Pharmacol. 2003 Mar 1;65(5):843-56
references.pmid: 12628479
references.citation: J Biol Chem. 2002 Nov 8;277(45):42781-9
references.pmid: 12202492
references.citation: Neuron. 2004 Jan 22;41(2):193-202
references.pmid: 14741101
references.citation: Neurosci Lett. 2002 May 10;324(1):83-5
references.pmid: 11983301
references.citation: Int J Neurosci. 2009;119(10):1881-904
references.pmid: 19922391
references.citation: J Biol Chem. 2004 Apr 2;279(14):14009-15
references.pmid: 14709547
references.citation: Am J Physiol. 1982 Sep;243(3):C161-8
references.pmid: 7114247
references.citation: Lipids. 1973 Nov;8(11):635-40
references.pmid: 4752499
references.citation: Ann Neurol. 1990 May;27(5):457-64
references.pmid: 2360787
references.citation: Neurosci Lett. 1999 Apr 23;265(3):218-22
references.pmid: 10327170
references.citation: Stroke. 2002 Apr;33(4):1152-62
references.pmid: 11935076
references.citation: J Lipid Res. 2004 Aug;45(8):1375-97
references.pmid: 15254070
references.citation: Acta Neuropathol. 1999 Apr;97(4):359-68
references.pmid: 10208275
references.citation: Annu Rev Neurosci. 1996;19:53-77
references.pmid: 8833436
references.citation: Atherosclerosis. 1984 Feb;50(2):133-46
references.pmid: 6712767
references.citation: Neurosci Lett. 1992 Feb 3;135(2):235-8
references.pmid: 1625800
references.citation: Arch Neurol. 2007 Feb;64(2):261-5
references.pmid: 17296843
references.citation: Biochem J. 2000 Jun 1;348 Pt 2:359-65
references.pmid: 10816430
references.citation: Psychosom Med. 1969 Mar-Apr;31(2):115-28
references.pmid: 5783999
references.citation: Am J Pathol. 1999 Feb;154(2):601-11
references.pmid: 10027417
references.citation: Biosci Biotechnol Biochem. 2006 Feb;70(2):447-56
references.pmid: 16495662
references.citation: Curr Opin Lipidol. 2001 Apr;12(2):105-12
references.pmid: 11264981
references.citation: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5815-20
references.pmid: 11309494
references.citation: Neuroscience. 2000;97(4):685-92
references.pmid: 10842013
references.citation: Neurobiol Dis. 1999 Feb;6(1):63-75
references.pmid: 10078974
references.citation: N Engl J Med. 1991 Dec 12;325(24):1704-8
references.pmid: 1944471
references.citation: J Neurosci. 2000 Mar 1;20(5):2064-71
references.pmid: 10684907
references.citation: J Neurol Sci. 2001 Jun 15;187(1-2):81-9
references.pmid: 11440749
references.citation: Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):832-9
references.pmid: 10195906
references.citation: Atherosclerosis. 1997 Aug;133(1):51-9
references.pmid: 9258407
references.citation: Am J Epidemiol. 1990 Mar;131(3):423-33
references.pmid: 2301352
references.citation: J Clin Invest. 1997 Dec 1;100(11):2671-9
references.pmid: 9389730
references.citation: Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):247-51
references.pmid: 7749833
references.citation: Neuroepidemiology. 1998;17(1):14-20
references.pmid: 9549720
references.citation: J Mol Neurosci. 2001 Oct;17(2):147-55
references.pmid: 11816788
references.citation: Life Sci. 2007 Jun 27;81(3):198-203
references.pmid: 17574275
references.citation: Pharmacol Ther. 2005 Jan;105(1):7-21
references.pmid: 15626453
references.citation: JAMA. 1994 May 4;271(17):1317
references.pmid: 7880218
references.citation: Am J Epidemiol. 2003 Jun 1;157(11):1007-14
references.pmid: 12777364
references.citation: Nature. 1994 Nov 3;372(6501):92-4
references.pmid: 7969426
references.citation: Am J Epidemiol. 2006 Nov 15;164(10):998-1002
references.pmid: 16905642
references.citation: J Clin Invest. 2008 Dec;118(12):4002-13
references.pmid: 19033669
references.citation: Nutr Rev. 1993 Aug;51(8):246-53
references.pmid: 8302497
references.citation: Biochim Biophys Acta. 1995 Mar 16;1255(2):192-200
references.pmid: 7696334
references.citation: Stroke. 2006 May;37(5):1184-8
references.pmid: 16574924
references.citation: Br J Psychiatry. 1993 Jun;162:818-25
references.pmid: 7980726
references.citation: Biochem Biophys Res Commun. 2006 Mar 31;342(1):9-18
references.pmid: 16466690
references.citation: Exp Neurol. 2005 Feb;191(2):318-25
references.pmid: 15649487
references.citation: Lancet Neurol. 2004 Mar;3(3):184-90
references.pmid: 14980533
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2892-7
references.pmid: 10694577
references.citation: J Lipid Res. 2004 Jan;45(1):186-93
references.pmid: 14523054
references.citation: Brain Res. 1998 Mar 30;788(1-2):151-9
references.pmid: 9554991
references.citation: Am J Med Genet. 1994 May 1;50(4):353-4
references.pmid: 8209914
references.citation: J Neurochem. 2008 Jul;106(1):475-85
references.pmid: 18410513
references.citation: Exp Neurol. 1997 Feb;143(2):313-8
references.pmid: 9056393
references.citation: Neuroreport. 1997 Jul 28;8(11):2505-10
references.pmid: 9261817
references.citation: Brain Res. 1987 Apr;429(2):271-81
references.pmid: 3567665
references.citation: Exp Gerontol. 1987;22(5):339-49
references.pmid: 3428411
references.citation: Nat Rev Neurosci. 2003 Feb;4(2):103-12
references.pmid: 12563281
references.citation: J Occup Environ Med. 1995 Jul;37(7):856-61
references.pmid: 7552471
references.citation: Arteriosclerosis. 1985 Nov-Dec;5(6):623-30
references.pmid: 4074195
references.citation: Life Sci. 2005 Sep 9;77(17):2156-65
references.pmid: 15935403
references.citation: Neurobiol Dis. 2002 Feb;9(1):11-23
references.pmid: 11848681
references.citation: Lancet. 1997 Jan 18;349(9046):151-4
references.pmid: 9111537
references.citation: J Psychiatr Res. 2000 Jul-Oct;34(4-5):301-9
references.pmid: 11104842
references.citation: Genome Res. 2000 Oct;10(10):1532-45
references.pmid: 11042151
references.citation: J Intern Med. 1997 Sep;242(3):199-211
references.pmid: 9350164
references.citation: Arch Neurol. 2003 Feb;60(2):194-200
references.pmid: 12580703
references.citation: J Am Geriatr Soc. 2004 Sep;52(9):1442-8
references.pmid: 15341544
references.citation: J Neurochem. 2009 Apr;109(1):125-34
references.pmid: 19166509
references.citation: Cell Mol Life Sci. 2009 Jul;66(13):2037-47
references.pmid: 19308323
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):443-8
references.pmid: 16407166
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13878-83
references.pmid: 12368482
references.citation: Biochem J. 1997 Mar 15;322 ( Pt 3):893-8
references.pmid: 9148766
references.citation: Neuron. 1995 Jul;15(1):219-28
references.pmid: 7619525
references.citation: Neurology. 1993 Aug;43(8):1467-72
references.pmid: 8350998
references.citation: J Pathol. 2001 Sep;195(2):244-50
references.pmid: 11592105
references.citation: Cell Mol Life Sci. 2003 Jun;60(6):1158-71
references.pmid: 12861382
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644-51
references.pmid: 16567625
references.citation: Metabolism. 2000 Apr;49(4):492-8
references.pmid: 10778874
references.citation: Neurosci Lett. 1996 Jun 14;211(1):41-4
references.pmid: 8809843
references.citation: Arterioscler Thromb. 1993 Jul;13(7):1013-8
references.pmid: 8391309
references.citation: J Intern Med. 2006 Dec;260(6):493-508
references.pmid: 17116000
references.citation: Am J Dis Child. 1989 May;143(5):537-42
references.pmid: 2718985
references.citation: Brain Res Dev Brain Res. 2003 Dec 19;146(1-2):87-98
references.pmid: 14643015
references.citation: Biol Psychiatry. 1984 Mar;19(3):435-9
references.pmid: 6722234
references.citation: Ann N Y Acad Sci. 2000 Apr;903:167-75
references.pmid: 10818504
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1930-4
references.pmid: 11172053
references.citation: Glia. 2004 Aug 15;47(3):209-16
references.pmid: 15252809
references.citation: Annu Rev Neurosci. 1999;22:11-28
references.pmid: 10202530
references.citation: Stroke. 1988 Sep;19(9):1097-100
references.pmid: 3413806
references.citation: Int J Biol Sci. 2009 Jun 29;5(5):474-88
references.pmid: 19584955
references.citation: Proc Natl Acad Sci U S A. 1979 Sep;76(9):4646-9
references.pmid: 291993
references.citation: J Neuroimmunol. 2007 Mar;184(1-2):69-91
references.pmid: 17222916
references.citation: Adv Lipid Res. 1965;3:171-96
references.pmid: 5331619
references.citation: Neuron. 2002 Aug 1;35(3):419-32
references.pmid: 12165466
references.citation: Pharmacopsychiatry. 2003 Sep;36 Suppl 2:S102-6
references.pmid: 14574622
references.citation: J Mol Neurosci. 2004;23(3):255-62
references.pmid: 15181254
references.citation: J Neurosci. 2003 Apr 15;23(8):3262-71
references.pmid: 12716933
references.citation: Atherosclerosis. 1989 Sep;79(1):79-83
references.pmid: 2803348
references.citation: J Neurosci. 2002 Dec 15;22(24):10539-48
references.pmid: 12486146
references.citation: Neurol Res. 2004 Jul;26(5):573-8
references.pmid: 15265277
references.citation: J Clin Endocrinol Metab. 1999 Apr;84(4):1296-303
references.pmid: 10199770
references.citation: J Neurochem. 1994 Nov;63(5):1802-11
references.pmid: 7931336
references.citation: J Neurosci. 2001 Feb 1;21(3):812-22
references.pmid: 11157067
references.citation: Exp Neurol. 1994 Mar;126(1):88-94
references.pmid: 8157129
references.citation: FEBS Lett. 1990 Aug 20;269(1):15-8
references.pmid: 2387395
references.citation: Neurology. 2000 Jan 11;54(1):240-2
references.pmid: 10636159
references.citation: J Cell Physiol. 1997 Oct;173(1):73-83
references.pmid: 9326451