Heterogeneity of elderly depression: Increased risk of Alzheimer's disease and Aβ protein metabolism

Namekawa, Yuki; Baba, Hajime; Maeshima, Hitoshi; Nakano, Yoshitaka; Satomura, Emi; Takebayashi, Naoko; Nishimura, Hiroshi; Suzuki, Tomohiko; Arai, Heii

doi:10.1016/j.pnpbp.2012.12.016

Cited by 39 publications

(36 citation statements)

References 71 publications

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“…to intraparenchymal Aβ administration and moving from short-term-acting oligomers to long-term affecting fibril forms (Shankar et al 2008). Clinical studies suggest that Aβ disturbances are associated with anxiety and depressive disorders (Harkany et al 2001;Sun et al 2008;Pomara et al 2014;Namekawa et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation

et al. 2015

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Neurodegenerative disorders are generally characterized by abnormal aggregation and deposition of specific proteins. Amyloid beta (Aβ)-associated neurodegenerative disorder is characterized by an oxidative damage that, in turn, leads to some behavioral changes before the establishment of dementia such as depression and anxiety. In the current study, we investigated the effect of heat shock protein 90 inhibitor geldanamycin (GA) administration 24 h before Aβ injection. In our experiment, 7 days after Aβ injection, elevated plus maze and forced swimming test were conducted to assess anxiety and depression-like behaviors. Levels of autophagy markers and malondialdehyde (MDA) and also activity of catalase in the hippocampus of rats were evaluated. Our behavioral analyses demonstrated that GA pretreatment can significantly decrease anxiety- and depression-like behaviors in Aβ-injected rats. Also, levels of autophagy markers including Atg12, Atg7, and LC3-II increased, while MDA level decreased and the activity of catalase increased in rats pretreated with GA compared to Aβ-injected rats. Thus, we assumed that GA, at least in part, ameliorated Aβ-mediated anxiety and depression by inducing autophagy and improving antioxidant defense system.

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Section: Discussionmentioning

confidence: 99%

Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation

et al. 2015

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“…In this regard, studies have found higher serum Aβ40/Aβ42 ratio in depression, compared with the controls (Baba 2010;Baba et al 2012). Importantly, the serum Aβ40/Aβ42 ratio was negatively correlated with the age of onset of MDD (Namekawa et al 2013). There is evidence that neuroplasticity is impaired in depression (Batsikadze et al 2013;Player et al 2013).…”

Section: Late-life Depressionmentioning

confidence: 94%

“…Several studies have documented upregulated Aβ metabolism in depression. Higher plasma Aβ40/42 ratio in late-onset depression suggests this to be prodromal manifestation of AD (Baba 2010;Baba et al 2012;Namekawa et al 2013). Even younger subjects with depression show pathological plasma Aβ40/42 ratio (Baba 2010;Baba et al 2012;Namekawa et al 2013).…”

Section: Depression: Prodromal To Admentioning

confidence: 99%

“…Higher plasma Aβ40/42 ratio in late-onset depression suggests this to be prodromal manifestation of AD (Baba 2010;Baba et al 2012;Namekawa et al 2013). Even younger subjects with depression show pathological plasma Aβ40/42 ratio (Baba 2010;Baba et al 2012;Namekawa et al 2013). It needs to be emphasized that quantitated CSF levels of these measures were similar in patients with major depression or AD (Hock et al 1998).…”

Section: Depression: Prodromal To Admentioning

confidence: 99%

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

Daulatzai

2014

Current Topics in Behavioral Neurosciences

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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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“…The neuropsychiatric symptoms and behavioral anomalies of AD have a significant impact on patient QOL and are thought to be predictive of eventual (or more severe) dementia [17, 18], more extensive neurodegeneration [19], loss of functional independence and institutionalization [20], and early death [21]. Thus, there is general agreement that these neuropsychiatric symptoms and behavioral anomalies are predictive of poor outcome, although symptom incidence, progression, and prognostic significance are highly variable across studies, possibly due to the different neuropsychiatric instruments used or clinical definitions.…”

Section: Introductionmentioning

confidence: 99%

Behavioral and Psychological Symptoms in Alzheimer’s Disease

Tan

et al. 2014

BioMed Research International

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Neuropsychiatric symptoms (NPS) such as depression, apathy, aggression, and psychosis are now recognized as core features of Alzheimer's disease (AD), and there is a general consensus that greater symptom severity is predictive of faster cognitive decline, loss of independence, and even shorter survival. Whether these symptoms result from the same pathogenic processes responsible for cognitive decline or have unique etiologies independent of AD-associated neurodegeneration is unclear. Many structural and metabolic features of the AD brain are associated with individual neuropsychiatric symptoms or symptom clusters. In addition, many genes have been identified and confirmed that are associated with symptom risk in a few cases. However, there are no single genes strongly predictive of individual neuropsychiatric syndromes, while functional and structural brain changes unique to specific symptoms may reflect variability in progression of the same pathological processes. Unfortunately, treatment success for these psychiatric symptoms may be lower when comorbid with AD, underscoring the importance of future research on their pathobiology and treatment. This review summarizes some of the most salient aspects of NPS pathogenesis.

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Heterogeneity of elderly depression: Increased risk of Alzheimer's disease and Aβ protein metabolism

Cited by 39 publications

References 71 publications

Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation

Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation

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

Behavioral and Psychological Symptoms in Alzheimer’s Disease

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