Extra-cranial factors in the development of Alzheimer's disease

被引:7
作者
Eiser, Arnold R. [1 ]
Fulop, Tamas [2 ]
机构
[1] Univ Penn, Leonard Davis Inst, 3641 Locust Wally, Philadelphia, PA 19104 USA
[2] Univ Sherbrooke, Res Ctr Aging, Med & Geriatr, Sherbrooke, PQ, Canada
关键词
Alzheimer's disease; Multi-organ disorder; Gut dysbiosis; Hepatic dysfunction; Dehydroepiandrosterone; Insulin resistance; Neuro-inflammation; NF-kB; NF-KAPPA-B; DOCOSAHEXAENOIC ACID; METABOLIC SYNDROME; DEHYDROEPIANDROSTERONE DHEA; COGNITIVE FUNCTION; DIABETES-MELLITUS; NERVOUS-SYSTEM; GUT-MICROBIOTA; AMYLOID-BETA; INSULIN;
D O I
10.1016/j.brainres.2020.147076
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The development of Alzheimer's Disease (AD) likely involves dysfunction in more than one extra-cranial organ system. AD appears to depend on several functional organ impairments that develops frequently during aging: lack of normal hepatic synthesis, defective detoxification of ammonia, gut microbiome dysbiosis, the development of insulin resistance, diminished adrenal production of dehydroepiandrosterone, nutrient depletion, impaired immune processes with persistent chronic neuro-inflammation, and persistent infectious processes are important components of this system-wide disorder. By reviewing these abnormalities in different organ systems, this review intends to suggest that clinical research into the prevention of dementia needs to take this interplay of organ system dysfunction into account. The design of therapeutic interventions needs to address dysfunction in more than one system at a time. We have singled out one aberrant signaling pathway, NF-kB, that seems common to several of the dysfunctional organ systems and suggest some potential interventions that may be effective when combined with others. Clinical research may need to shift from single factor interventions to studies that include multiple simultaneous interventions that restore health in multiple impaired organ systems in the aging human in order to avert future epidemics of AD.
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页数:6
相关论文
共 78 条
[71]   Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise [J].
van Dyck, Christopher H. .
BIOLOGICAL PSYCHIATRY, 2018, 83 (04) :311-319
[72]   Effect of DHEA on abdominal fat and insulin action in elderly women and men - A randomized controlled trial [J].
Villareal, DT ;
Holloszy, JO .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 292 (18) :2243-2248
[73]   Gut microbiome alterations in Alzheimer's disease [J].
Vogt, Nicholas M. ;
Kerby, Robert L. ;
Dill-McFarland, Kimberly A. ;
Harding, Sandra J. ;
Merluzzi, Andrew P. ;
Johnson, Sterling C. ;
Carlsson, Cynthia M. ;
Asthana, Sanjay ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Bendlin, Barbara B. ;
Rey, Federico E. .
SCIENTIFIC REPORTS, 2017, 7
[74]  
Xu L, 2018, J ALZHEIMERS DIS, V62, P361, DOI [10.3233/jad-170811, 10.3233/JAD-170811]
[75]   NSAID Exposure and Risk of Alzheimer's Disease: An Updated Meta-Analysis From Cohort Studies [J].
Zhang, Caixia ;
Wang, Yan ;
Wang, Dongyin ;
Zhang, Jidong ;
Zhang, Fangfang .
FRONTIERS IN AGING NEUROSCIENCE, 2018, 10
[76]   Blockade of interleukin-6 receptor in the periphery promotes rapid and sustained antidepressant actions: a possible role of gut-microbiota-brain axis [J].
Zhang, J-C ;
Yao, W. ;
Dong, C. ;
Yang, C. ;
Ren, Q. ;
Ma, M. ;
Hashimoto, K. .
TRANSLATIONAL PSYCHIATRY, 2017, 7 :e1138-e1138
[77]   Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link [J].
Zhang, Ying ;
Huang, Nan-qu ;
Yan, Fei ;
Jin, Hai ;
Zhou, Shao-yu ;
Shi, Jing-shan ;
Jin, Feng .
BEHAVIOURAL BRAIN RESEARCH, 2018, 339 :57-65
[78]   Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain [J].
Zwain, IH ;
Yen, SSC .
ENDOCRINOLOGY, 1999, 140 (08) :3843-3852