Amyloid‐β and islet amyloid pathologies link Alzheimer’s disease and type 2 diabetes in a transgenic model

Epidemiological studies have shown that the development of Alzheimer's disease (AD) is associated with type 2 diabetes (T2D), but it still remains unclear how AD and T2D are connected.

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Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

International Journal of Molecular Sciences ◽

10.3390/ijms19113306 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3306 ◽

Cited By ~ 39

Author(s):

Andrea Tumminia ◽

Federica Vinciguerra ◽

Miriam Parisi ◽

Lucia Frittitta

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Type 2 Diabetes Mellitus ◽

Cell Activation ◽

Insulin Signalling ◽

Amyloid Β ◽

Neuronal Stem Cell

In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer’s disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.

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Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22115603 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5603

Author(s):

Anna Litwiniuk ◽

Wojciech Bik ◽

Małgorzata Kalisz ◽

Agnieszka Baranowska-Bik

Keyword(s):

Alzheimer’S Disease ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Chronic Inflammation ◽

Amyloid Β ◽

Inflammatory Factors ◽

Low Grade ◽

Neurodegenerative Dementia

Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.

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A Relationship Between Alzheimer's Disease and Type 2 Diabetes Mellitus Through the Measurement of Serum Amyloid-β Autoantibodies

Journal of Alzheimer s Disease ◽

10.3233/jad-2010-1332 ◽

2010 ◽

Vol 19 (4) ◽

pp. 1371-1376 ◽

Cited By ~ 15

Author(s):

Insub Kim ◽

Junhee Lee ◽

Hyun Joo Hong ◽

Eun Sun Jung ◽

Yun Hyi Ku ◽

...

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Type 2 Diabetes Mellitus ◽

Amyloid Β ◽

Serum Amyloid

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Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

Current Diabetes Reviews ◽

10.2174/1573399816999201012200537 ◽

2020 ◽

Vol 16 ◽

Author(s):

Nataly Guzmán-Herrera ◽

Viridiana C. Pérez-Nájera ◽

Luis A. Salazar-Olivo

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Regulatory Networks ◽

Therapeutic Strategies ◽

Oxidative Stresses ◽

Bibliographic Search ◽

And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

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Establishing Genomic/Transcriptomic Links Between Alzheimer’s Disease and Type 2 Diabetes Mellitus by Meta-Analysis Approach

CNS & Neurological Disorders - Drug Targets ◽

10.2174/18715273113126660154 ◽

2014 ◽

Vol 13 (3) ◽

pp. 501-516 ◽

Cited By ~ 17

Author(s):

Zeenat Mirza ◽

Mohammad Kamal ◽

Adel buzenadah ◽

Mohammed Al-Qahtani ◽

Sajjad Karim

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Type 2 Diabetes Mellitus ◽

Meta Analysis ◽

Analysis Approach

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Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽

10.3390/cells10051236 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1236

Author(s):

Jesús Burillo ◽

Patricia Marqués ◽

Beatriz Jiménez ◽

Carlos González-Blanco ◽

Manuel Benito ◽

...

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Type 2 Diabetes Mellitus ◽

Insulin Signaling ◽

Molecular Mechanisms ◽

Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

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