APOE genotype and sex modulate Alzheimer's disease pathology in aged EFAD transgenic mice

被引:9
|
作者
Balu, Deebika [1 ]
Valencia-Olvera, Ana C. [1 ]
Islam, Zarak [1 ,2 ]
Mielczarek, Clare [1 ]
Hansen, Allison [1 ,3 ]
Ramos, Tamara M. Perez [1 ,4 ]
York, Jason [1 ]
Ladu, Mary Jo [1 ]
Tai, Leon M. [1 ]
机构
[1] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60607 USA
[2] Univ Illinois, Coll Med, Chicago, IL USA
[3] Univ Illinois, Coll Med Peoria, Peoria, IL USA
[4] St Georges Univ, Sch Med, St Georges, Grenada
来源
FRONTIERS IN AGING NEUROSCIENCE | 2023年 / 15卷
基金
美国国家卫生研究院;
关键词
Alzheimer's disease; APOE4; female risk; transgenic mice; amyloid-beta; APOLIPOPROTEIN-E GENOTYPE; A-BETA ACCUMULATION; COGNITIVE DECLINE; MOUSE MODEL; TYPE-4; ALLELE; GENETIC RISK; ONSET; ASSOCIATION; EPSILON-4; IMPAIRMENT;
D O I
10.3389/fnagi.2023.1279343
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Increasing evidence supports that age, APOE and sex interact to modulate Alzheimer's disease (AD) risk, however the underlying pathways are unclear. One way that AD risk factors may modulate cognition is by impacting amyloid beta (A beta) accumulation as plaques, and/or neuroinflammation Therefore, the goal of the present study was to evaluate the extent to which age, APOE and sex modulate A beta pathology, neuroinflammation and behavior in vivo. To achieve this goal, we utilized the EFAD mice, which express human APOE3 or APOE4 and have five familial AD mutations (FAD) that result in A beta 42 overproduction. We assessed A beta levels, reactive glia and Morris water maze performance in 6-, 10-, 14-, and 18-month-old EFAD mice. Female APOE4 mice had the highest A beta deposition, fibrillar amyloid deposits and neuroinflammation as well as earlier behavior deficits. Interestingly, we found that female APOE3 mice and male APOE4 mice had similar levels of pathology. Collectively our data support that the combination of APOE4 and female sex is the most detrimental combination for AD, and that at older ages, female sex may be equivalent to APOE4 genotype.
引用
收藏
页数:11
相关论文
共 50 条
  • [41] APOE genotype effects on alzheimer’s disease onset and epidemiology
    J. Wesson Ashford
    Journal of Molecular Neuroscience, 2004, 23 : 157 - 165
  • [42] The association between APOE genotype and progression of Alzheimer's disease
    Tsolaki, M.
    Bosiki, M.
    Daniilidou, M.
    Pitsalidis, C. H.
    Molyva, D.
    Kounti, F.
    Papassotiropoulos, A.
    Kazis, A.
    EUROPEAN JOURNAL OF NEUROLOGY, 2005, 12 : 58 - 58
  • [43] APOE genotype and survival in men and women with Alzheimer's disease
    Dal Forno, G
    Carson, KA
    Brookmeyer, R
    Troncoso, J
    Kawas, CH
    Brandt, J
    NEUROLOGY, 2002, 58 (07) : 1045 - 1050
  • [44] The Association of Essential Metals with APOE Genotype in Alzheimer's Disease
    Leko, Mirjana Babic
    Jurasovic, Jasna
    Perkovic, Matea Nikolac
    Spanic, Ena
    Sekovanic, Ankica
    Orct, Tatjana
    Skudar, Vesna Lukinovic
    Baronica, Koraljka Bacic
    Kidemet-Piskac, Spomenka
    Vogrinc, Zeljka
    Pivac, Nela
    Borovecki, Fran
    Hof, Patrick R.
    Simic, Goran
    JOURNAL OF ALZHEIMERS DISEASE, 2021, 82 (02) : 661 - 672
  • [45] Prediction of APOE genotype by phenotype in Alzheimer's disease.
    Todd, RD
    Ji, T
    Goate, AM
    AMERICAN JOURNAL OF MEDICAL GENETICS, 1998, 81 (06): : 554 - 554
  • [46] APOE genotype, lipids and risk for Alzheimer's disease in the Yoruba
    Ogunniyi, A
    Hall, KS
    Murrell, J
    Baiyewu, O
    Deeg, M
    Gureje, O
    Gao, S
    Unverzagt, FW
    Shen, J
    Smith-Gamble, V
    Dickson, J
    Hendrie, HC
    JOURNAL OF THE NEUROLOGICAL SCIENCES, 2005, 238 : S296 - S296
  • [47] Phenotype of depression in Alzheimer's disease (AD) with APOE genotype
    Cantillon, M
    Barker, W
    Harwood, D
    Mullan, M
    Duara, R
    BIOLOGICAL PSYCHIATRY, 1996, 39 (07) : 546 - 546
  • [48] The APOE Genotype: Modification of Therapeutic Responses in Alzheimer's Disease
    Hanson, Angela J.
    Craft, Suzanne
    Banks, William A.
    CURRENT PHARMACEUTICAL DESIGN, 2015, 21 (01) : 114 - 120
  • [49] APOE genotype effects on Alzheimer's disease onset and epidemiology
    Ashford, JW
    JOURNAL OF MOLECULAR NEUROSCIENCE, 2004, 23 (03) : 157 - 165
  • [50] Cognitive impairment in Alzheimer's disease is modified by APOE genotype
    van der Vlies, Annelies E.
    Pijnenburg, Yolande A. L.
    Koene, Teddy
    Klein, Martin
    Kok, Astrid
    Scheltens, Philip
    van der Flier, Wiesje M.
    DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2007, 24 (02) : 98 - 103