Current Alzheimer Research - Volume 16, Issue 12, 2019

Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Methods: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

Background: Alzheimer's Disease (AD) is often accompanied by severe sleep problems and circadian rhythm disturbances which may to some extent be attributed to a dysfunction in the biological clock. The 24-h light/dark cycle is the strongest Zeitgeber for the biological clock. People with AD, however, often live in environments with inappropriate photic Zeitgebers. Timed bright light exposure may help to consolidate sleep- and circadian rest/activity rhythm problems in AD, and may be a low-risk alternative to pharmacological treatment. Objective & Methods: In the present review, experts from several research disciplines summarized the results of twenty-seven light intervention studies which used wrist actigraphy to measure sleep and circadian activity in AD patients. Results: Taken together, the findings remain inconclusive with regard to beneficial light effects. However, the considered studies varied substantially with respect to the utilized light intervention, study design, and usage of actigraphy. The paper provides a comprehensive critical discussion of these issues. Conclusion: Fusing knowledge across complementary research disciplines has the potential to critically advance our understanding of the biological input of light on health and may contribute to architectural lighting designs in hospitals, as well as our homes and work environments.

A variety of neurological diseases, including Alzheimer’s disease (AD), involve amyloid beta (Aβ) accumulation and/or neuroinflammation, which can alter synaptic and neural circuit functions. Consequently, these pathological conditions induce changes in neural network rhythmic activity (brain arrhythmias), which affects many brain functions. Neural network rhythms are involved in information processing, storage and retrieval, which are essential for memory consolidation, executive functioning and sensory processing. Therefore, brain arrhythmias could have catastrophic effects on circuit function, underlying the symptoms of various neurological diseases. Moreover, brain arrhythmias can serve as biomarkers for a variety of brain diseases. The aim of this review is to provide evidence linking Aβ and inflammation to neural network dysfunction, focusing on alterations in brain rhythms and their impact on cognition and sensory processing. I reviewed the most common brain arrhythmias characterized in AD, in AD transgenic models and those induced by Aβ. In addition, I reviewed the modulations of brain rhythms in neuroinflammatory diseases and those induced by immunogens, interleukins and microglia. This review reveals that Aβ and inflammation produce a complex set of effects on neural network function, which are related to the induction of brain arrhythmias and hyperexcitability, both closely related to behavioral alterations. Understanding these brain arrhythmias can help to develop therapeutic strategies to halt or prevent these neural network alterations and treat not only the arrhythmias but also the symptoms of AD and other inflammation-related pathologies.

Background: Alzheimer’s Disease (AD) is the most common neurodegenerative disorder, and it is still incurable. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. Mounting evidence indicates that the neurotoxic effects might be attributed to Soluble β-Amyloid Oligomers (SAβO). The SAβO are believed to be neurotoxic peptides more predominant than Aβ plaques in the early stage, and their key role in AD is self-evident. Unfortunately, identification of SAβO proves to be difficult due to their heterogeneous and transient nature. In spite of many obstacles, multiple techniques have recently been developed to target SAβO effectively. This review focuses on the recent progress in the approaches towards SAβO detection in order to shed some light on the future development of SAβO assays. Methods: Literatures were obtained from the following libraries: Web of Science, PubMed, EPO, SIPO, USPTO. Articles were critically reviewed based on their titles, abstracts, and contents. Results: A total of 85 papers are referenced in the review. Results are divided into three categories based on the types of detection methods: small molecule fluorescence probes, oligomer-specific antibodies and electrochemical biosensors. Finally, the improvements and challenges of these approaches applied in the early diagnosis of AD were discussed. Conclusion: This review article covers three kinds of strategies that could be translated into clinic practice and lead to earlier diagnosis and therapeutic interventions of AD.

Background/Aims: Recent evidence has shown that Alzheimer’s Disease (AD) patients have reduced vestibular function relative to healthy controls. In this study, we evaluated whether patients with Mild Cognitive Impairment (MCI) also have reduced vestibular function relative to controls, and compared the level of vestibular impairment between MCI and AD patients. Methods: Vestibular physiologic function was assessed in 77 patients (26 MCI, 51 AD) and 295 matched controls using 3 clinical vestibular tests. The association between vestibular loss and cognitive impairment was evaluated using conditional logistic regression models. Results: Individuals with vestibular impairment had a 3 to 4-fold increased odds of being in the MCI vs. control group (p-values < 0.05). MCI patients had a level of vestibular impairment that was intermediate between controls and AD. Conclusion: These findings suggest a dose-response relationship between vestibular loss and cognitive status, and support the hypothesis that vestibular loss contributes to cognitive decline.

Background: Glycogen Synthase Kinase (GSK)-3β and Brain-derived Neurotrophic Factor (BDNF) play vital roles in both Mild Cognitive Impairment (MCI) and Type 2 Diabetes Mellitus (T2DM). The underlying mechanisms may involve inflammation and oxidative stress. Objectives: To investigate the association of the GSK-3β/BDNF ratio with MCI in elderly patients with T2DM and whether GSK-3β/BDNF ratio can serve as a new diagnostic biomarker for MCI in comorbid with T2DM (MD). Methods: A total of 326 old Chinese T2DM patients were included and stratified according to cognition and GSK-3β/BDNF ratio quartiles. MCI was diagnosed according to the National Institute on Aging Alzheimer’s Association workgroups criteria. In addition to routine hematuria and biochemical examinations, Montreal Cognitive Assessment (MoCA) scale was also used to evaluate the cognitive function, and ELISA method was used to measure GSK-3β activity and the serum levels of BDNF, interleukin 1β (IL-1β), high mobility group box-1 (HMGB1) protein, Malonaldehyde (MDA) and 8-isoprostaglandinF2α (8-iso-PGF2α). Results: We found that GSK-3β activity was negatively correlated with BDNF (r=-0.270, P=0.008), and patients with higher GSK-3β/BDNF ratio had lower MoCA scores (P=0.001). When compared with T2DM patients without MCI (nMD), MD patients had higher GSK-3β activity and GSK-3β/BDNF ratio, but lower BDNF levels. As for inflammation and oxidative stress, IL-1β was inversely correlated with GSK-3β activity, while 8-isoPGF2α was positively correlated with GSK-3β activity and GSK-3β/BDNF ratio. The odds ratio for MCI increased gradually when GSK-3β/BDNF ratio quartile rose from the lowest to the highest (6.90, 95% CI 3.22-14.78). MoCA score was conversely related to GSK-3β/BDNF ratio, age and fast blood glucose (FBG), with GSK-3β/BDNF ratio having the most significant influence on cognition (β=-0.199, P<0.001). Conclusion: Our data provide evidence for a strong link between GSK-3β/BDNF ratio and MCI. GSK- 3β/BDNF ratio may serve as a better diagnostic biomarker for MD than either GSK-3β or BDNF alone and increased GSK-3β/BDNF ratio indicates a worse cognitive function.