Environmental factors in the development and progression of late-onset Alzheimer’s disease

Moses N Wainaina; Zhichun Chen; Chunjiu Zhong

doi:10.1007/s12264-013-1425-9

. 2014 Mar 24;30(2):253–270. doi: 10.1007/s12264-013-1425-9

Environmental factors in the development and progression of late-onset Alzheimer’s disease

Moses N Wainaina ^1,³, Zhichun Chen ¹, Chunjiu Zhong ^1,^2,^✉

PMCID: PMC5562669 PMID: 24664867

Abstract

Late-onset Alzheimer’s disease (LOAD) is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.

Keywords: Alzheimer’s disease, environmental factors, corticotrophin-releasing factor, cerebrovascular, metal toxicity, glia, astrocyte, microglia, Aβ, kinase, phosphatase, tau, hyperphosphorylation, epigenetic modification, DNA methylation, histone acetylation

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PERMALINK

Environmental factors in the development and progression of late-onset Alzheimer’s disease

Moses N Wainaina

Zhichun Chen

Chunjiu Zhong

Abstract

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Environmental factors in the development and progression of late-onset Alzheimer’s disease

Moses N Wainaina

Zhichun Chen

Chunjiu Zhong

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