Rethinking Alzheimer’s disease: The role of age-related changes

AbstractThe negative association between Alzheimer’s disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising.

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Neuroimaging Approaches for Elderly Studies

Medical Imaging ◽

10.4018/978-1-5225-0571-6.ch067 ◽

2017 ◽

pp. 1576-1617

Author(s):

Charis Styliadis ◽

Panagiotis Kartsidis ◽

Evangelos Paraskevopoulos

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Structure And Function ◽

Cognitive Capacity ◽

Aging Brain ◽

Cerebral Structure ◽

Age Related ◽

Elderly Populations ◽

And Function ◽

Age Related Changes

Advances in the field of neuroimaging have allowed for the examination of the effects of age-related changes on cognitive capacity in elderly populations. Structural techniques are now routinely used to report cortical atrophic rates in aging and particularly within the context of the Alzheimer's disease, and may be integrated with functional techniques which examine the functional characteristics of the cortex at rest and during the performance of a task. Despite advancing age cognitive function remains highly plastic, allowing for interventions that aim to maintain or even remediate its capacity and the mechanisms by which structure and function are altered among seniors. Overall, information on the integrity of the cerebral structure and function aid in the early detection and treatment of the Alzheimer's disease as well as the evaluation and track of the disease's progression. In this chapter, neuroimaging methods are presented along with findings that are particularly relevant for the study of neuroplasticity in the aging brain.

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The effect of preclinical Alzheimer's disease on age-related changes in intelligence in cognitively normal older adults

Intelligence ◽

10.1016/j.intell.2018.07.004 ◽

2018 ◽

Vol 70 ◽

pp. 22-29 ◽

Cited By ~ 2

Author(s):

Karra D. Harrington ◽

Christa Dang ◽

Yen Ying Lim ◽

David Ames ◽

Simon M. Laws ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Preclinical Alzheimer’S Disease ◽

Cognitively Normal ◽

Age Related ◽

Age Related Changes

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Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽

10.3390/cells8090968 ◽

2019 ◽

Vol 8 (9) ◽

pp. 968 ◽

Cited By ~ 6

Author(s):

Sunitha Kodidela ◽

Kelli Gerth ◽

Sanjana Haque ◽

Yuqing Gong ◽

Saifudeen Ismael ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Extracellular Vesicles ◽

Treatment Strategies ◽

Progressive Dementia ◽

Hiv Patients ◽

Age Related ◽

Infected Cells ◽

New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

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Zinc-mediated Neurotransmission in Alzheimer's Disease: A Potential Role of the GPR39 in Dementia

Current Neuropharmacology ◽

10.2174/1570159x17666190704153807 ◽

2019 ◽

Vol 18 (1) ◽

pp. 2-13

Author(s):

Michal Rychlik ◽

Katarzyna Mlyniec

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Neural Plasticity ◽

Modern Society ◽

Neuroprotective Drugs ◽

Age Related ◽

Candidate Drug ◽

G Protein Coupled

: With more people reaching an advanced age in modern society, there is a growing need for strategies to slow down age-related neuropathology and loss of cognitive functions, which are a hallmark of Alzheimer's disease. Neuroprotective drugs and candidate drug compounds target one or more processes involved in the neurodegenerative cascade, such as excitotoxicity, oxidative stress, misfolded protein aggregation and/or ion dyshomeostasis. A growing body of research shows that a G-protein coupled zinc (Zn2+) receptor (GPR39) can modulate the abovementioned processes. : Zn2+itself has a diverse activity profile at the synapse, and by binding to numerous receptors, it plays an important role in neurotransmission. However, Zn2+ is also necessary for the formation of toxic oligomeric forms of amyloid beta, which underlie the pathology of Alzheimer’s disease. Furthermore, the binding of Zn2+ by amyloid beta causes a disruption of zincergic signaling, and recent studies point to GPR39 and its intracellular targets being affected by amyloid pathology. : In this review, we present neurobiological findings related to Zn2+ and GPR39, focusing on its signaling pathways, neural plasticity, interactions with other neurotransmission systems, as well as on the effects of pathophysiological changes observed in Alzheimer's disease on GPR39 function. : Direct targeting of the GPR39 might be a promising strategy for the pharmacotherapy of zincergic dyshomeostasis observed in Alzheimer’s disease. The information presented in this article will hopefully fuel further research into the role of GPR39 in neurodegeneration and help in identifying novel therapeutic targets for dementia.

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P1-176 Age-related changes of Alzheimer's disease-associated protein in cynomolgus monkey brains

Neurobiology of Aging ◽

10.1016/s0197-4580(04)80489-5 ◽

2004 ◽

Vol 25 ◽

pp. S145-S146

Author(s):

Nobuyuki Kimura ◽

Kentaro Tanemura ◽

Shin-Ichiro Nakamura ◽

Akihiko Takashima ◽

Katsuhiko Yanagisawa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cynomolgus Monkey ◽

Age Related ◽

Age Related Changes

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Overview of Alzheimer’s Disease and Some Therapeutic Approaches Targeting Aβby Using Several Synthetic and Herbal Compounds

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/7361613 ◽

2016 ◽

Vol 2016 ◽

pp. 1-22 ◽

Cited By ~ 50

Author(s):

Sandeep Kumar Singh ◽

Saurabh Srivastav ◽

Amarish Kumar Yadav ◽

Saripella Srikrishna ◽

George Perry

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Models ◽

Neurodegenerative Disease ◽

Therapeutic Approaches ◽

Age Related

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-βmetabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics.

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