Alzheimer’s Disease: The Past, Present, and Future of a Globally Progressive Disease

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 5, 2024

Alzheimer's disease (AD) is a significant 21st-century public health challenge. This article delves into AD's neurodegenerative complexities, highlighting cognitive decline, memory impairment, and societal burdens. Mechanistically, protein misfolding, amyloid-beta (Aβ) pathway abnormalities, genetic/environmental factors are discussed. The pivotal amyloid hypothesis dissected, focusing on Aβ aggregation's role in synaptic dysfunction neurodegeneration. review showcases promising therapeutic strategies, including anti-amyloid antibodies β/γ-secretase inhibitors targeting production. Notably, the FDA-approved Lecanemab signifies breakthrough, slowing progression. Anti-Tau therapies' emergence highlighted, addressing late-stage intervention. Tau aggregation blockers anti-Tau offer potential against intracellular tau pathology. underscores collaborative efforts to uncover secrets pave way for preservation.

Language: Английский

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Cholecystokinin (CCK): a neuromodulator with therapeutic potential in Alzheimer’s and Parkinson’s disease

Frontiers in Neuroendocrinology, Journal Year: 2024, Volume and Issue: 73, P. 101122 - 101122

Published: Feb. 11, 2024

Cholecystokinin (CCK) is a neuropeptide modulating digestion, glucose levels, neurotransmitters and memory. Recent studies suggest that CCK exhibits neuroprotective effects in Alzheimer's disease (AD) Parkinson's (PD). Thus, we review the physiological function therapeutic potential of CCK. The facilitates hippocampal glutamate release gates GABAergic basket cell activity, which improves declarative memory acquisition, but inhibits consolidation. Cortical alters recognition enhances audio-visual processing. By stimulating CCK-1 receptors (CCK-1Rs), sulphated CCK-8 elicits dopamine substantia nigra striatum. In mesolimbic pathway, triggered by terminates reward responses via CCK-2Rs. Importantly, activation nigral CCK-2Rs evoking AMPK activation, expression mitochondrial fusion modulators autophagy. Other benefits include vagus nerve/CCK-1R-mediated brain-derived neurotrophic factor, intestinal protection suppression inflammation. We also discuss caveats combination with other peptide hormones.

Language: Английский

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Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3278 - 3278

Published: Feb. 7, 2023

A decrease in the activity of insulin signaling system brain, due to both central resistance and deficiency, leads neurodegeneration impaired regulation appetite, metabolism, endocrine functions. This is neuroprotective properties brain its leading role maintaining glucose homeostasis as well network responsible for functioning nervous, endocrine, other systems. One approaches restore use intranasally administered (INI). Currently, INI being considered a promising drug treat Alzheimer’s disease mild cognitive impairment. The clinical application developed treatment neurodegenerative diseases improve abilities stress, overwork, depression. At same time, much attention has recently been paid prospects using cerebral ischemia, traumatic injuries, postoperative delirium (after anesthesia), diabetes mellitus complications, including dysfunctions gonadal thyroid axes. review devoted current trends these diseases, which, although differing etiology pathogenesis, are characterized by brain.

Language: Английский

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Diet’s Role in Modifying Risk of Alzheimer’s Disease: History and Present Understanding

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 96(4), P. 1353 - 1382

Published: Nov. 7, 2023

Diet is an important nonpharmacological risk-modifying factor for Alzheimer's disease (AD). The approaches used here to assess diet's role in the risk of AD include multi-country ecological studies, prospective and cross-sectional observational laboratory studies. Ecological studies have identified fat, meat, obesity from high-energy diets as factors reported that rates peak about 15-20 years after national dietary changes. Observational compared Western pattern with those Dietary Approaches Stop Hypertension (DASH), Mediterranean (MedDi), Mediterranean-DASH Intervention Neurodegenerative Delay (MIND) diets. Those including higher consumption saturated total fats, ultraprocessed foods a lower fruits, legumes, nuts, omega-3 fatty acids, vegetables, whole grains. Diet-induced associated significant inflammation, insulin resistance, oxidative stress, elevated homocysteine, advanced glycation end products, trimethylamine N-oxide. molecular mechanisms by which bioactive components specific affect are discussed. Given most countries' entrenched food supply systems, upward trends would be hard reverse. However, people willing able, low-animal product diet plenty anti-inflammatory, low-glycemic load may helpful.

Language: Английский

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Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 183 - 183

Published: Jan. 16, 2023

Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates AD is a significant comorbidity of T2D, there ~1.4–2-fold increase risk developing among T2D patients, involvement possible common triggers pathogenesis these two remains largely unknown. Of note, recent mechanistic insights suggest lipotoxicity could missing ring pathogenetic mechanisms linking to AD. Indeed, obesity, which represents main cause lipotoxicity, has been recognized as factor for both pathological conditions. Lipotoxicity can lead inflammation, insulin resistance, oxidative stress, ceramide amyloid accumulation, endoplasmic reticulum ferroptosis, autophagy, are shared biological events In current review, we try provide critical comprehensive view molecular pathways activated by AD, attempting summarize how drive future research open way new therapeutic perspectives.

Language: Английский

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Expanding the Role of Continuous Glucose Monitoring in Modern Diabetes Care Beyond Type 1 Disease

Diabetes Therapy, Journal Year: 2023, Volume and Issue: 14(8), P. 1241 - 1266

Published: June 16, 2023

Application of continuous glucose monitoring (CGM) has moved diabetes care from a reactive to proactive process, in which person with can prevent episodes hypoglycemia or hyperglycemia, rather than taking action only once low and high are detected. Consequently, CGM devices now seen as the standard for people type 1 mellitus (T1DM). Evidence supports use 2 (T2DM) on any treatment regimen, not just those insulin therapy. Expanding application include all T1DM T2DM support effective intensification therapies reduce exposure lower risk complications hospital admissions, associated healthcare costs. All this be achieved while minimizing improving quality life diabetes. Wider also bring considerable benefits women during pregnancy their children, well providing acute inpatients who experience adverse effects hyperglycemia following admission surgical procedures, consequence treatment-related resistance reduced secretion. By tailoring daily intermittent use, depending patient profile needs, one ensure cost-effectiveness each setting. In article we discuss evidence-based expanding technology diabetes, along diverse population non-diabetic glycemic dysregulation.

Language: Английский

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The roles of dietary polyphenols at crosstalk between type 2 diabetes and Alzheimer's disease in ameliorating oxidative stress and mitochondrial dysfunction via PI3K/Akt signaling pathways

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102416 - 102416

Published: July 13, 2024

Language: Английский

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Alzheimer’s Disease as Type 3 Diabetes: Understanding the Link and Implications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11955 - 11955

Published: Nov. 7, 2024

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as "type 3 diabetes", highlighting the critical roles insulin resistance impaired glucose metabolism pathogenesis disease. This article examines implications this association, exploring potential new avenues for treatment preventive strategies AD. Key evidence linking to emphasizes metabolic processes contribute neurodegeneration, including inflammation, oxidative stress, alterations signaling pathways. By framing within context, we can enhance our understanding its etiology, which turn may influence early diagnosis, plans, measures. Understanding manifestation opens up possibility employing therapeutic incorporate lifestyle modifications use antidiabetic medications mitigate cognitive decline. integrated approach improve patient outcomes deepen comprehension intricate relationship between neurodegenerative diseases disorders.

Language: Английский

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Neuronal CD59 isoforms IRIS-1 and IRIS-2 as regulators of neurotransmitter release with implications for Alzheimer’s disease

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 7, 2025

Abstract We have previously demonstrated that the intracellular, non-GPI anchored CD59 isoforms IRIS-1 and IRIS-2 (Isoforms Rescuing Insulin Secretion 1 2) are necessary for insulin secretion from pancreatic β-cells. While investigating their expression across human tissues, we identified mRNA in brain, though protein function remained unclear. This study shows presence of both 2 proteins specifically neurons astrocytes. In neuroblastoma cell line (SH-SY5Y), increases upon differentiation into mature neurons. Silencing SH-SY5Y cells reduces SNARE complex formation, essential synaptic vesicle exocytosis, leading to a reduction noradrenaline secretion. Notably, observed diminished neuronal patients with Alzheimer’s disease (AD) non-demented individuals type diabetes (T2D). cells, knockdown all including not only elevates phosphorylated tau but also cyclin-dependent kinase 5 (CDK5) expression, known promoter hyperphosphorylation accumulation tau, key pathological feature AD. Additionally, found prolonged exposure high glucose or cytokines markedly suggesting link between AD pathology metabolic stress through modulation these isoforms.

Language: Английский

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Quantitative Assessment of the Effect of Chronic Kidney Disease on Plasma P-Tau217 Concentrations

Neurology, Journal Year: 2025, Volume and Issue: 104(3)

Published: Jan. 17, 2025

Chronic kidney disease (CKD) is known to be associated with increased plasma phosphorylated tau217 (p-tau217) concentrations, potentially confounding the utility of p-tau217 measurements as a marker amyloid pathology in individuals suspected Alzheimer (AD). In this study, we quantitatively investigate relationship concentrations vs estimated glomerular filtration rate (eGFR) CKD and without pathology. This was retrospective examination data from 2 observational cohorts either Mayo Clinic Study Aging or Alzheimer's Disease Research Center cohorts. p-Tau217 determined using ALZpath Simoa immunoassay an immunoprecipitation mass spectrometry assay that simultaneously measures nonphosphorylated-tau217 (np-tau217) determine %p-tau217 ([p-tau217/nonphosphorylated-tau217]) × 100%) (C2N Diagnostics). Amyloid positivity defined by amyloid-PET centiloid ≥25. Log-log linear regression fits were used predict increases decreasing eGFR. Participants (n = 202, mean age 78 years, 38% female) diagnoses cognitive unimpairment 109), mild impairment 71), dementia 22) included. all, 114 (56%) all participants positive (A+). addition, 86 (43%) classified having (CKD stages 3-4). significantly higher A- eGFR <60 (mL/min/1.73 m2), compared those >60 participants. For 45 60 cohort, calculated percentage changes +31%, +55%, +19%, for p-tau217, C2N %p-tau217, respectively. A+ corresponding +17%, +15%, -5%, when measuring methodologies, but effect mitigated use %p-tau217. These results indicate limitations significant renal (eGFR <45 stage 3b greater). Determination should considered avoid inaccurate classification presence AD-related CKD. study provides Class II evidence 3 (especially 3b) higher, are increased, greater increase amyloid-PET-negative individuals.

Language: Английский

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