Role of apolipoprotein E in anxiety.
Anxiety is most common among Alzheimer's disease (AD) patients with an age at onset under age 65. Apolipoprotein E4 (apoE4) is a risk factor for developing AD at an earlier age and might contribute to this effect. In mice, apoE plays a role in the regulation of anxiety, which might involve histamine receptor-mediated signaling and steroidogenesis in the adrenal gland. In addition, human apoE isoforms have differential effects on anxiety in adult mice lacking apoE and probable AD patients. Compared to wild-type mice, mice lacking apoE and apoE4 mice showed pathological alterations in the central nucleus of the amygdala, which is involved in regulation of anxiety. ApoE4, but not mice lacking apoE, or apoE3 mice showed impaired dexamethasone suppression of plasma corticosterone. Understanding how apoE modulates measures of anxiety might help the developments of therapeutic targets to reduce or even prevent measures of anxiety in health and in dementing illnesses.
Raber
Jacob
J
Department of Behavioral Neuroscience, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, L470, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D000679:Amygdala / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D053318:Apolipoprotein E3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053327:Apolipoprotein E4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4
J Neurosci. 2000 Mar 1;20(5):2064-71
10684907
Nat Neurosci. 2000 Mar;3(3):238-44
10700255
Am J Geriatr Psychiatry. 2000 Summer;8(3):196-200
10910416
J Biol Chem. 2000 Nov 24;275(47):36781-6
10973974
Pharmacol Biochem Behav. 2000 Sep;67(1):145-50
11113494
Psychol Med. 2001 Apr;31(3):431-40
11305851
Alzheimer Dis Assoc Disord. 1994;8(Suppl. 1):S360-7
11657168
Neurology. 2002 Apr 23;58(8):1182-8
11971084
Biol Psychiatry. 2002 Jun 1;51(11):875-81
12022960
J Neurosci. 2002 Jun 15;22(12):5204-9
12077215
Neurology. 2002 Sep 10;59(5):746-8
12221169
J Neuropsychiatry Clin Neurosci. 2003 Spring;15(2):180-6
12724459
J Gerontol Nurs. 2004 Jan;30(1):12-20
14753054
Neuropsychopharmacology. 2004 Mar;29(3):441-9
14628000
Rev Neurol. 2004 May 16-31;38(10):901-5
15175968
Neurology. 2004 Jun 8;62(11):1990-5
15184602
J Alzheimers Dis. 2004 Jun;6(3):329-36
15201487
JAMA. 1982 Jul 16;248(3):333-5
7087127
Br J Psychiatry. 1983 Sep;143:277-81
6626841
Neurology. 1984 Jul;34(7):939-44
6610841
Biol Psychiatry. 1985 Jan;20(1):86-93
3965040
Science. 1988 Apr 29;240(4852):622-30
3283935
Br J Psychiatry. 1991 Jan;158:64-71
2015452
J Gerontol. 1991 Nov;46(6):P362-71
1940093
J Lipid Res. 1991 Oct;32(10):1611-8
1665849
Mol Endocrinol. 1992 Feb;6(2):288-98
1373819
Life Sci. 1993;53(22):1675-83
8231648
J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):644-9
8648331
Neurology. 1996 Jul;47(1):256-9
8710089
Methods Find Exp Clin Pharmacol. 1996 Jan-Feb;18(1):19-24
8721252
Brain Behav Immun. 1996 Jun;10(2):115-25
8811935
J Neural Transm Suppl. 1996;47:205-18
8841967
J Clin Endocrinol Metab. 1997 Oct;82(10):3251-9
9329348
JAMA. 1997 Oct 22-29;278(16):1349-56
9343467
Mol Neurobiol. 1998 Aug;18(1):1-22
9824846
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15049-54
9844013
Biol Psychiatry. 1999 Feb 15;45(4):422-5
10071711
Am J Geriatr Psychiatry. 1999 Spring;7(2):119-23
10322238
Neurobiol Aging. 2005 May;26(5):637-43
15708438