Exercise as Potential Therapeutic Target to Modulate Alzheimer's Disease Pathology in APOE ε4 Carriers: A Systematic Review

被引:26
作者
Tokgoz, Sevilay [1 ,2 ]
Claassen, Jurgen A. H. R. [1 ,2 ,3 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands
[2] Radboudumc Alzheimer Ctr, Dept Geriatr Med, Nijmegen, Netherlands
[3] Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands
关键词
Alzheimer’ s disease; APOE4; genotype; Exercise intervention; Mild cognitive impairment; Physical activity; BETA-AMYLOID DEPOSITION; PHYSICAL-ACTIVITY; APOLIPOPROTEIN-E; A-BETA; LIFE-STYLE; COGNITIVE FUNCTION; OLDER-ADULTS; MOUSE MODEL; CHOLESTEROL-METABOLISM; DECREASED CLEARANCE;
D O I
10.1007/s40119-020-00209-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective treatment exists at present. Previous research has found that exercise reduces the risk of AD. Since the apolipoprotein E (APOE) epsilon 4 allele increases the risk of AD and is associated with faster disease progression than the other isoforms, we aimed to highlight the impact of exercise on AD pathology in APOE epsilon 4 carriers. This review focuses on the effect of exercise on cognitive function, dementia risk, amyloid-beta (A beta) metabolism, lipid metabolism, neuroinflammation, neurotrophic factors and vascularization in APOE epsilon 4 carriers. We searched the literature in the PubMed electronic database using the following search terms: physical activity, exercise, aerobic fitness, training, sport, APOE4, Alzheimer's disease, AD and dementia. By cross-referencing, additional publications were identified. Selected studies required older adults to take part in an exercise intervention or to make use of self-reported physical activity questionnaires. All included studies were written and published in English between 2000 and 2020. From these studies, we conclude that exercise is a non-pharmacological treatment option for high-risk APOE epsilon 4 carriers to ameliorate the AD pathological processes including reducing A beta load, protecting against hippocampal atrophy, improving cognitive function, stabilizing cholesterol levels and lowering pro-inflammatory signals. Variation in study design related to age, cognitive outcomes and the type of intervention explained the differences in study outcomes. However, exercise seems to be effective in delaying the onset of AD and may improve the quality of life of AD patients.
引用
收藏
页码:67 / 88
页数:22
相关论文
共 96 条
[1]   Molecular Insight into the Therapeutic Promise of Targeting APOE4 for Alzheimer's Disease [J].
Al Mamun, Abdullah ;
Uddin, Md Sahab ;
Bin Bashar, Md Fahim ;
Zaman, Sonia ;
Begum, Yesmin ;
Bulbul, Israt Jahan ;
Islam, Md Siddiqul ;
Sarwar, Md Shahid ;
Mathew, Bijo ;
Amran, Md Shah ;
Ashraf, Ghulam Md ;
Bin-Jumah, May N. ;
Mousa, Shaker A. ;
Abdel-Daim, Mohamed M. .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2020, 2020
[2]   APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study [J].
Allard, Joanne S. ;
Ntekim, Oyonumo ;
Johnson, Steven P. ;
Ngwa, Julius S. ;
Bond, Vernon ;
Pinder, Dynell ;
Gillum, Richard F. ;
Fungwe, Thomas V. ;
Kwagyan, John ;
Obisesan, Thomas O. .
EXPERIMENTAL GERONTOLOGY, 2017, 87 :129-136
[3]   Reduction of amyloid angiopathy and Aβ plaque burden after enriched housing in TgCRND8 mice -: Involevement of multiple pathways [J].
Ambree, Oliver ;
Leimer, Uwe ;
Herring, Arne ;
Goertz, Nicole ;
Sachser, Norbert ;
Heneka, Michael T. ;
Paulus, Werner ;
Keyvani, Kathy .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 169 (02) :544-552
[4]   Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo [J].
Bateman, Randall J. ;
Munsell, Ling Y. ;
Morris, John C. ;
Swarm, Robert ;
Yarasheski, Kevin E. ;
Holtzman, David M. .
NATURE MEDICINE, 2006, 12 (07) :856-861
[5]   Apolipoprotein E controls cerebrovascular integrity via cyclophilin A [J].
Bell, Robert D. ;
Winkler, Ethan A. ;
Singh, Itender ;
Sagare, Abhay P. ;
Deane, Rashid ;
Wu, Zhenhua ;
Holtzman, David M. ;
Betsholtz, Christer ;
Armulik, Annika ;
Sallstrom, Jan ;
Berk, Bradford C. ;
Zlokovic, Berislav V. .
NATURE, 2012, 485 (7399) :512-516
[6]   Age-related differences in memory and executive functions in healthy APOE ε4 carriers: The contribution of individual differences in prefrontal volumes and systolic blood pressure [J].
Bender, Andrew R. ;
Raz, Naftali .
NEUROPSYCHOLOGIA, 2012, 50 (05) :704-714
[7]   Physical activity may modulate effects of ApoE genotype on lipid profile [J].
Bernstein, MS ;
Costanza, MC ;
James, RW ;
Morris, MA ;
Cambien, F ;
Raoux, S ;
Morabia, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (01) :133-140
[8]   PHYSICAL ACTIVITY, INFLAMMATION, AND VOLUME OF THE AGING BRAIN [J].
Braskie, M. N. ;
Boyle, C. P. ;
Rajagopalan, P. ;
Gutman, B. A. ;
Toga, A. W. ;
Raji, C. A. ;
Tracy, R. P. ;
Kuller, L. H. ;
Becker, J. T. ;
Lopez, O. L. ;
Thompson, P. M. .
NEUROSCIENCE, 2014, 273 :199-209
[9]   Physical activity and amyloid-β plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing [J].
Brown, B. M. ;
Peiffer, J. J. ;
Taddei, K. ;
Lui, J. K. ;
Laws, S. M. ;
Gupta, V. B. ;
Taddei, T. ;
Ward, V. K. ;
Rodrigues, M. A. ;
Burnham, S. ;
Rainey-Smith, S. R. ;
Villemagne, V. L. ;
Bush, A. ;
Ellis, K. A. ;
Masters, C. L. ;
Ames, D. ;
Macaulay, S. L. ;
Szoeke, C. ;
Rowe, C. C. ;
Martins, R. N. .
MOLECULAR PSYCHIATRY, 2013, 18 (08) :875-881
[10]   Using network science to evaluate exercise-associated brain changes in older adults [J].
Burdette, Jonathan H. ;
Laurienti, Paul J. ;
Espeland, Mark A. ;
Morgan, Ashley ;
Telesford, Qawi ;
Vechlekar, Crystal D. ;
Hayasaka, Satoru ;
Jennings, Janine M. ;
Katula, Jeffrey A. ;
Kraft, Robert A. ;
Rejeski, W. Jack .
FRONTIERS IN AGING NEUROSCIENCE, 2010, 2