Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative.
More than 5 million Americans are living with Alzheimer's disease (AD) today, and nearly two-thirds of Americans with AD are women. This sex difference may be due to the higher longevity women generally experience; however, increasing evidence suggests that longevity alone is not a sufficient explanation and there may be other factors at play. The Alzheimer's Association convened an expert think tank to focus on the state of the science and level of evidence around gender and biological sex differences for AD, including the knowledge gaps and areas of science that need to be more fully addressed. This article summarizes the think tank discussion, moving forward a research agenda and funding program to better understand the biological underpinnings of sex- and gender-related disparities of risk for AD.
Division of Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA. Electronic address: hsnyder@alz.org.
Heather M
HM
Snyder
Department of Medicine, University of Wisconsin School of Medicine, Madison, WI, USA.
Sanjay
S
Asthana
Independent Science Writer, Philadelphia, PA, USA.
Lisa
L
Bain
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA; Department of Neurology, University of Southern California, Los Angeles, CA, USA.
Roberta
R
Brinton
Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Suzanne
S
Craft
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Dena B
DB
Dubal
Department of Biostatistical Science, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Mark A
MA
Espeland
Department of Psychology, University of Southern California, Los Angeles, CA, USA.
Margaret
M
Gatz
Division of Epidemiology, Department of Health Sciences Research and Neurology, Mayo Clinic, Rochester, MN, USA.
Michelle M
MM
Mielke
Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, Oregon Health & Science University, Portland, OR, USA; Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR, USA.
Jacob
J
Raber
Laboratory of Behavioral Neuroscience, Neurocognitive Aging Section, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
Peter R
PR
Rapp
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
Kristine
K
Yaffe
Division of Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA.
Maria C
MC
Carrillo
D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology*; D004198:Disease Susceptibility / Q000503:physiopathology*; D005260:Female; D006801:Humans; D012307:Risk Factors; D012727:Sex Characteristics; D012737:Sex Factors; D012958:Societies, Scientific
APOE; Alzheimer's disease; Estrogen; Hormones; Neurodegeneration; Risk factors; Sex biology; Women
Neuropsychopharmacology. 2015 Sep;40(10):2443-53
25857685
J Womens Health (Larchmt). 2008 Sep;17(7):1191-9
18710367
Biol Sex Differ. 2012 Nov 05;3(1):24
23126652
Pharmacol Rev. 2010 Jun;62(2):155-98
20392807
Front Neuroendocrinol. 2014 Jan;35(1):8-30
23994581
Neurobiol Aging. 2005 May;26(5):637-43
15708438
Front Aging Neurosci. 2015 Jul 07;7:130
26217222
JAMA. 2013 Oct 2;310(13):1353-68
24084921
J Alzheimers Dis. 2012;31(2):401-10
22571978
Neurology. 2002 Aug 13;59(3):364-70
12177369
Alzheimers Dement. 2015 May;11(5):504-510.e1
25043908
Ann Neurol. 2014 Apr;75(4):563-73
24623176
Neurology. 2016 Aug 16;87(7):699-708
27421538
J Neurochem. 2003 Nov;87(4):1052-5
14622134
J Neurochem. 2008 Apr;105(1):63-7
18039320
Am J Epidemiol. 1998 Mar 15;147(6):574-80
9521184
JAMA. 1997 Oct 22-29;278(16):1349-56
9343467
Obstet Gynecol Clin North Am. 2011 Sep;38(3):567-86
21961720
J Neuroendocrinol. 2008 Jun;20(6):866-72
18513207
Neurology. 2015 Sep 29;85(13):1131-8
26163429
N Engl J Med. 2013 Dec 12;369(24):2275-7
24283198
Trends Neurosci. 2008 Oct;31(10):529-37
18774188
Biochim Biophys Acta. 2010 Oct;1800(10):1121-6
20538040
J Gerontol A Biol Sci Med Sci. 2017 Jun 01;72(6):838-845
27506836
J Neurosci. 2006 Aug 30;26(35):9047-56
16943563
Neurology. 2000 Jun 13;54(11):2072-7
10851365
Nature. 2000 Mar 23;404(6776):352-4
10746713
J Neurobiol. 2005 Jul;64(1):34-46
15884004
Horm Behav. 2014 Sep;66(4):602-18
25205317
Br J Psychiatry. 1995 Aug;167(2):255-62
7582679
Front Biosci (Elite Ed). 2012 Jan 01;4(3):976-97
22201929
Science. 2009 Nov 13;326(5955):1005-7
19779148
Neuroimage. 2013 Jan 15;65:176-93
23063452
J Am Geriatr Soc. 2008 Jan;56(1):45-50
18047498
Neurobiol Aging. 2015 Apr;36(4):1751-1756
25670333
EMBO J. 2015 Jun 12;34(12):1674-86
25964433
Nat Rev Endocrinol. 2015 Jul;11(7):393-405
26007613
JAMA Intern Med. 2013 Aug 12;173(15):1429-36
23797469
Menopause. 2013 Jun;20(6):695-709
23715379
J Neurochem. 2005 Sep;94(6):1639-51
16011741
Neurology. 2002 Jan 22;58(2):209-18
11805246
Biol Psychiatry. 2010 Mar 15;67(6):505-12
19358976
Science. 1993 Aug 13;261(5123):921-3
8346443
Biochim Biophys Acta. 2010 Oct;1800(10):1113-20
19931595
EBioMedicine. 2015 Dec 12;3:26-42
26870815
Nat Rev Neurol. 2013 Feb;9(2):106-18
23296339
J Neurosci. 2012 Jun 13;32(24):8254-62
22699906
JAMA. 2004 Jun 23;291(24):2947-58
15213206
J Neurosci. 2010 Sep 22;30(38):12770-6
20861381
Neuroimage. 2011 Jun 1;56(3):890-906
21356315
J Neurosci. 2010 Jan 13;30(2):431-8
20071507
J Neurol Sci. 2005 Mar 15;229-230:43-9
15760618
Arch Neurol. 2005 May;62(5):779-84
15883266
Atherosclerosis. 2015 Jul;241(1):219-28
25817330
Clin Epidemiol. 2014 Jan 08;6:37-48
24470773
Biol Psychiatry. 2015 Jan 1;77(1):43-51
24951455
Cochrane Database Syst Rev. 2015 Apr 22;(4):CD005381
25900537
Alzheimers Dement. 2014 Mar;10(2):e47-92
24818261
Brain Struct Funct. 2015 Mar;220(2):861-8
24343570
Front Neuroendocrinol. 2011 Apr;32(2):227-46
20951723
Biol Sex Differ. 2012 Aug 21;3(1):19
22908911
Oncotarget. 2015 Sep 29;6(29):26663-74
26397226
PLoS One. 2013 Sep 11;8(9):e74915
24040361
Alzheimers Dement. 2015 Mar;11(3):310-320
24418058
Neurology. 2001 Mar 13;56(5):650-4
11245718
Am J Epidemiol. 2014 Aug 15;180(4):414-23
24859276
Neurology. 2014 Feb 11;82(6):504-11
24477111
Trends Pharmacol Sci. 2009 Apr;30(4):212-22
19299024
J Alzheimers Dis. 2015;44(3):897-906
25374101
Neurodegener Dis. 2010;7(1-3):163-6
20197698
Br J Psychiatry. 2000 Dec;177:486-92
11102321
Biol Psychiatry. 2007 Oct 15;62(8):847-55
17544382
J Neurosci. 2002 Jun 15;22(12):5204-9
12077215
J Clin Endocrinol Metab. 2008 Apr;93(4):1339-44
18230654
Biol Psychol. 2005 Apr;69(1):113-32
15740829
J Neurosci. 2003 Jul 2;23(13):5708-14
12843274
Psychol Rev. 2008 Apr;115(2):291-313
18426291
Arch Neurol. 2007 Jan;64(1):93-6
17210814
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10914-9
9724804
Neurology. 2004 Oct 12;63(7):1187-92
15477536
JAMA. 2004 Sep 22;292(12):1431-2
15383512
Ann Intern Med. 2004 Apr 6;140(7):501-9
15068977
BMJ Open. 2013 Sep 30;3(9):e003142
24080094
J Neuroendocrinol. 2007 Feb;19(2):77-81
17214869
Arch Gen Psychiatry. 1999 May;56(5):425-30
10232297
Am J Hum Genet. 2013 May 2;92(5):643-7
23643377
PLoS One. 2013;8(2):e54713
23418430
J Epidemiol Community Health. 2014 Feb;68(2):151-8
24258197
J Neurosci. 2000 Mar 1;20(5):2064-71
10684907
Neurobiol Aging. 2015 Jul;36(7):2282-2295
25921624
Clin Endocrinol (Oxf). 2010 Jan;72(1):99-106
19508596
Diabetes Care. 2015 Dec;38(12):2316-24
26486190
Neuroimage. 2009 May 1;45(4):1107-16
19349228
Menopause. 2013 May;20(5):511-7
23615642
J Am Geriatr Soc. 2011 Jan;59(1):57-66
21226676
Front Neuroendocrinol. 2009 Jul;30(2):239-58
19427328
J Alzheimers Dis. 2010;20 Suppl 2:S527-33
20442496
Front Psychiatry. 2015 Mar 09;6:32
25806005
Endocr Rev. 2003 Apr;24(2):133-51
12700177
Cell Res. 2008 Nov;18(11):1141-50
18936784
Neurology. 1993 Mar;43(3 Pt 1):515-9
8450993
J Alzheimers Dis. 2013;35(4):789-97
23507773
Neurology. 2009 Jan 13;72(2):135-42
19139364
Biochim Biophys Acta. 2010 Oct;1800(10):1068-76
20100548
J Alzheimers Dis. 2008 Apr;13(3):323-31
18430999
JAMA. 2004 Jun 23;291(24):2959-68
15213207
J Clin Endocrinol Metab. 2003 Jun;88(6):2404-11
12788835
J Neurosci. 2016 Jan 20;36(3):901-10
26791219
J Alzheimers Dis. 2010;22(2):569-79
20847403
Neurology. 2012 Jan 31;78(5):342-51
22282647
J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):177-83
10071096
Alzheimers Dement. 2016 Apr;12(4):399-406
26549599
Endocr Rev. 2010 Apr;31(2):224-53
20019127
Neurology. 1997 Jan;48(1):132-8
9008508
Psychol Aging. 2016 Mar;31(2):166-75
26796792
Neurobiol Aging. 2012 Apr;33(4):829.e9-20
21855173
Brain Res. 2001 Nov 16;919(1):160-5
11689174
Am J Epidemiol. 2001 Jan 15;153(2):132-6
11159157
Neurology. 2008 Jan 15;70(3):191-9
18195264
PLoS Med. 2015 Jun 02;12(6):e1001833; discussion e1001833
26035291
Arch Neurol. 2011 Jan;68(1):51-7
20837822