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Role of Stress, Depression, and Aging in Cognitive Decline and Alzheimer’s Disease

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Behavioral Neurobiology of Stress-related Disorders

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 18))

Abstract

Late-onset Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the most common cause of progressive cognitive dysfunction and dementia. Despite considerable progress in elucidating the molecular pathology of this disease, we are not yet close to unraveling its etiopathogenesis. A battery of neurotoxic modifiers may underpin neurocognitive pathology via deleterious heterogeneous pathologic impact in brain regions, including the hippocampus. Three important neurotoxic factors being addressed here include aging, stress, and depression. Unraveling “upstream pathologies” due to these disparate neurotoxic entities, vis-à-vis cognitive impairment involving hippocampal dysfunction, is of paramount importance. Persistent systemic inflammation triggers and sustains neuroinflammation. The latter targets several brain regions including the hippocampus causing upregulation of amyloid beta and neurofibrillary tangles, synaptic and neuronal degeneration, gray matter volume atrophy, and progressive cognitive decline. However, what is the fundamental source of this peripheral inflammation in aging, stress, and depression? This chapter highlights and delineates the inflammatory involvement—i.e., from its inception from gut to systemic inflammation to neuroinflammation. It highlights an upregulated cascade in which gut-microbiota-related dysbiosis generates lipopolysaccharides (LPS), which enhances inflammation and gut’s leakiness, and through a Web of interactions, it induces stress and depression. This may increase neuronal dysfunction and apoptosis, promote learning and memory impairment, and enhance vulnerability to cognitive decline.

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Acknowledgments

I express my sincere gratitude to the following colleagues for their generosity in permitting me to use figures from their papers: Dr. Hiroshi Imaoka for Figure 1 and Dr. Mike McGrath for Fig. 2. Neela Khan of the Swinburne University, Victoria, Australia gave excellent help with EXCEL.

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  1. Sleep Disorders Group, EEE Department, Melbourne School of Engineering, The University of Melbourne, Building 193, 3rd Floor, Room no. 3/344, Parkville, VIC, 3010, Australia

    Mak Adam Daulatzai

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Correspondence to Mak Adam Daulatzai .

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  1. Department of Psychological Medicine, Institute of Psychiatry Kings College London, London, United Kingdom

    Carmine M. Pariante

  2. Family and Community Health Systems, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

    M. Danet Lapiz-Bluhm

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Daulatzai, M.A. (2014). Role of Stress, Depression, and Aging in Cognitive Decline and Alzheimer’s Disease. In: Pariante, C., Lapiz-Bluhm, M. (eds) Behavioral Neurobiology of Stress-related Disorders. Current Topics in Behavioral Neurosciences, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2014_350

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