Is Alzheimer's disease a systemic disease? - PubMed (original) (raw)
Review
Is Alzheimer's disease a systemic disease?
Jill K Morris et al. Biochim Biophys Acta. 2014 Sep.
Abstract
Although Alzheimer's disease (AD) is the most common neurodegenerative disease, the etiology of AD is not well understood. In some cases, genetic factors explain AD risk, but a high percentage of late-onset AD is unexplained. The fact that AD is associated with a number of physical and systemic manifestations suggests that AD is a multifactorial disease that affects both the CNS and periphery. Interestingly, a common feature of many systemic processes linked to AD is involvement in energy metabolism. The goals of this review are to 1) explore the evidence that peripheral processes contribute to AD risk, 2) explore ways that AD modulates whole-body changes, and 3) discuss the role of genetics, mitochondria, and vascular mechanisms as underlying factors that could mediate both central and peripheral manifestations of AD. Despite efforts to strictly define AD as a homogeneous CNS disease, there may be no single etiologic pathway leading to the syndrome of AD dementia. Rather, the neurodegenerative process may involve some degree of baseline genetic risk that is modified by external risk factors. Continued research into the diverse but related processes linked to AD risk is necessary for successful development of disease-modifying therapies.
Keywords: Alzheimer's disease; Exercise; Metabolism; Mitochondria; Physical activity.
Copyright © 2014 Elsevier B.V. All rights reserved.
Figures
Figure 1. Schematic of potential risk factors for AD
We propose that a combination of nuclear and mitochondrially-encoded genes determine one’s baseline risk for AD. This baseline risk can be modified – either increased (+) or decreased (−) by a wide variety of environmental factors, (diet, exercise) socioeconomic factors (i.e. education) and inevitably by the aging process.
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References
- Thies W, Bleiler L, Alzheimer’s A. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement. 2013;9(2):208–45. - PubMed
- Agosta F, Pievani M, Sala S, et al. White matter damage in Alzheimer disease and its relationship to gray matter atrophy. Radiology. 2011;258(3):853–63. - PubMed
- Backman L, Jones S, Berger AK, et al. Multiple cognitive deficits during the transition to Alzheimer’s disease. J Intern Med. 2004;256(3):195–204. - PubMed
- Riviere S, Gillette-Guyonnet S, Andrieu S, et al. Cognitive function and caregiver burden: predictive factors for eating behaviour disorders in Alzheimer’s disease. Int J Geriatr Psychiatry. 2002;17(10):950–5. - PubMed
- Johnson DK, Wilkins CH, Morris JC. Accelerated Weight Loss May Precede Diagnosis in Alzheimer Disease. Arch Neurol. 2006;63(9):1312–1317. - PubMed
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