TY - JOUR
T1 - Parallels Between Major Depressive Disorder and Alzheimer’s Disease
T2 - Role of Oxidative Stress and Genetic Vulnerability
AU - Rodrigues, Roberto
AU - Petersen, Robert B.
AU - Perry, George
N1 - Funding Information:
Acknowledgments George Perry is supported by the Semmes Foundation, Inc.; the Alzheimer Association; and by a grant from the National Institute on Minority Health and Health Disparities (G12MD007591) from the National Institutes of Health.
Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/10
Y1 - 2014/10
N2 - The thesis of this review is that oxidative stress is the central factor in major depressive disorder (MDD) and Alzheimer’s disease (AD). The major elements involved are inflammatory cytokines, the hypothalamic–pituitary axis, the hypothalamic–pituitary gonadal, and arginine vasopressin systems, which induce glucocorticoid and “oxidopamatergic” cascades when triggered by psychosocial stress, severe life-threatening events, and mental-affective and somatic diseases. In individuals with a genomic vulnerability to depression, these cascades may result in chronic depression–anxiety–stress spectra, resulting in MDD and other known depressive syndromes. In contrast, in subjects with genomic vulnerability to AD, oxidative stress-induced brain damage triggers specific antioxidant defenses, i.e., increased levels of amyloid-β (Aβ) and aggregation of hyper-phosphorylated tau, resulting in paired helical filaments and impaired functions related to the ApoEε4 isoform, leading to complex pathological cascades culminating in AD. Surprisingly, all the AD-associated molecular pathways mentioned in this review have been shown to be similar or analogous to those found in depression, including structural damage, i.e., hippocampal and frontal cortex atrophy. Other interacting molecular signals, i.e., GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD.
AB - The thesis of this review is that oxidative stress is the central factor in major depressive disorder (MDD) and Alzheimer’s disease (AD). The major elements involved are inflammatory cytokines, the hypothalamic–pituitary axis, the hypothalamic–pituitary gonadal, and arginine vasopressin systems, which induce glucocorticoid and “oxidopamatergic” cascades when triggered by psychosocial stress, severe life-threatening events, and mental-affective and somatic diseases. In individuals with a genomic vulnerability to depression, these cascades may result in chronic depression–anxiety–stress spectra, resulting in MDD and other known depressive syndromes. In contrast, in subjects with genomic vulnerability to AD, oxidative stress-induced brain damage triggers specific antioxidant defenses, i.e., increased levels of amyloid-β (Aβ) and aggregation of hyper-phosphorylated tau, resulting in paired helical filaments and impaired functions related to the ApoEε4 isoform, leading to complex pathological cascades culminating in AD. Surprisingly, all the AD-associated molecular pathways mentioned in this review have been shown to be similar or analogous to those found in depression, including structural damage, i.e., hippocampal and frontal cortex atrophy. Other interacting molecular signals, i.e., GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD.
KW - Alzheimer’s disease
KW - Amyloid β
KW - Lipid peroxidation
KW - Major depressive disorder
KW - Nucleic acid oxidation
KW - Oxidative stress
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=84930278819&partnerID=8YFLogxK
U2 - 10.1007/s10571-014-0074-5
DO - 10.1007/s10571-014-0074-5
M3 - Review article
C2 - 24927694
AN - SCOPUS:84930278819
VL - 34
SP - 925
EP - 949
JO - Cellular and Molecular Neurobiology
JF - Cellular and Molecular Neurobiology
SN - 0272-4340
IS - 7
ER -