Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease

Šimić, Goran; Španić, Ena; Horvat, Luka; Hof, Patrick R.

doi:10.1016/bs.pmbts.2019.06.003

Cited by 27 publications

(23 citation statements)

References 283 publications

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“…Furthermore, changes in neurophysiological processes, especially energy metabolism of the brain, occurred, but at a price [74,83]. Namely, an increase in aerobic metabolism leads to higher levels of oxidative stress, which favors the development of neurodegenerative diseases, and some of them can be seen only in humans, e.g., Alzheimer's disease [74,84]. Comparative studies have shown that the brain of an adult at rest consumes 20-25% of the body's metabolic energy, while other primates consume on average between 11 and 13%, and other mammals 2 to 8% [85].…”

Section: Neotenymentioning

confidence: 99%

Molecules, Mechanisms, and Disorders of Self-Domestication: Keys for Understanding Emotional and Social Communication from an Evolutionary Perspective

et al. 2020

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The neural crest hypothesis states that the phenotypic features of the domestication syndrome are due to a reduced number or disruption of neural crest cells (NCCs) migration, as these cells differentiate at their final destinations and proliferate into different tissues whose activity is reduced by domestication. Comparing the phenotypic characteristics of modern and prehistoric man, it is clear that during their recent evolutionary past, humans also went through a process of self-domestication with a simultaneous prolongation of the period of socialization. This has led to the development of social abilities and skills, especially language, as well as neoteny. Disorders of neural crest cell development and migration lead to many different conditions such as Waardenburg syndrome, Hirschsprung disease, fetal alcohol syndrome, DiGeorge and Treacher-Collins syndrome, for which the mechanisms are already relatively well-known. However, for others, such as Williams-Beuren syndrome and schizophrenia that have the characteristics of hyperdomestication, and autism spectrum disorders, and 7dupASD syndrome that have the characteristics of hypodomestication, much less is known. Thus, deciphering the biological determinants of disordered self-domestication has great potential for elucidating the normal and disturbed ontogenesis of humans, as well as for the understanding of evolution of mammals in general.

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Section: Neotenymentioning

confidence: 99%

Molecules, Mechanisms, and Disorders of Self-Domestication: Keys for Understanding Emotional and Social Communication from an Evolutionary Perspective

et al. 2020

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“…The concept of selective neuronal vulnerability refers to a situation where certain neurons are more vulnerable than others to pathogenic processes that cause the misfolding and aggregation of tau proteins. This is perhaps determined by biochemical, genomic, connectomic, electrophysiological, and morphological properties of vulnerable neurons (Šimić et al, 2017, 2019) and region-specific microenvironments (Jackson, 2014). There are other possible reasons for vulnerability due to differential protein expression: for example, in regions that are always affected by tau pathology, elevated expression of some proteins that co-aggregate with tau and Aβ, with lower expression of proteins that can prevent aggregation of tau and Aβ has been observed, when compared to regions less susceptible to the disease (Freer et al, 2016).…”

Section: Propagation Of Tau Proteinmentioning

confidence: 99%

“…Several lines of evidence suggest that inflammation may even precede the development of tau pathology (Yoshiyama et al, 2007; Denver and McClean, 2018). Therefore, controlling the components in a complex inflammatory process represents a new possible therapeutic approach for neurodegenerative diseases (for review see Šimić et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Role of Microglial Cells in Alzheimer’s Disease Tau Propagation

Španić

Horvat

Hof

et al. 2019

Front. Aging Neurosci.

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Uncontrolled immune response in the brain contributes to the progression of all neurodegenerative disease, including Alzheimer’s disease (AD). Recent investigations have documented the prion-like features of tau protein and the involvement of microglial changes with tau pathology. While it is still unclear what sequence of events is causal, it is likely that tau seeding potential and microglial contribution to tau propagation act together, and are essential for the development and progression of degenerative changes. Based on available evidence, targeting tau seeds and controlling some signaling pathways in a complex inflammation process could represent a possible new therapeutic approach for treating neurodegenerative diseases. Recent findings propose novel diagnostic assays and markers that may be used together with standard methods to complete and improve the diagnosis and classification of these diseases. In conclusion, a novel perspective on microglia-tau relations reveals new issues to investigate and imposes different approaches for developing therapeutic strategies for AD.

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“…Polymorphisms in IL-1β, IL-1α and IL-10 genes could lead to different transcription products and consequently influence the amount of the produced proteins [26][27][28][29][30]. Increase in production of pro-inflammatory cytokines (IL-1β and IL-1α) and decrease in production of anti-inflammatory cytokines (IL-10) would result in increased inflammation that favours development of AD [1,2,31]. We show that MMSE scores are significantly lower in carriers of a G allele in IL-1β -1473, T allele in IL-1α -889, and A allele in IL-10 -1082 polymorphisms, while P300 latency is significantly prolonged in carriers of a G allele in IL-1β -1473 polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Association of IL-1β, IL-1α and IL-10 single nucleotide polymorphisms with Mini-Mental State Examination and event-related potentials

Leko

Perković

Skorić

et al. 2019

Preprint

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Background: Neuroinflammation is enhanced in Alzheimer’s disease (AD) brain. Its association with both amyloid and tau pathology is well documented. Activated microglia in the AD brain release pro-inflammatory cytokines that can damage neurons, while anti-inflammatory cytokines are also released to oppose this process. Association of IL-1β -1473C/G, IL-1α -889C/T and IL-10 -1082G/A polymorphisms with AD has been amply documented previously. In this study we assessed whether people carrying certain genotypes in these polymorphisms were more prone to disease progression as tested by the Mini‐Mental State Examination (MMSE) scores and event-related potentials (ERP). Methods: After blood collection, isolation of DNA and determination of polymorphisms, 226 subjects were tested neuropsychologically using MMSE (including AD patients, mild cognitive impairment patients, patients with other causes of dementia, and healthy controls). ERP were measured by electroencephalography (EEG) in this cohort. Results: MMSE scores were significantly lower in patients carrying the G allele in the IL-1β -1473, T allele in the IL-1α -889, and A allele in the IL-10 -1082 polymorphism. The P300 latency was significantly prolonged in patients carrying the G allele in the IL-1β -1473 polymorphism. Conclusions: Patients carrying risk genotypes in IL-1β -1473, IL-1α -889 and IL-10 -1082 polymorphisms may be susceptible to faster disease progression. Additionally, IL-1β -1473 polymorphism may represent a strong genetic biomarker of AD.

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Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease

Cited by 27 publications

References 283 publications

Molecules, Mechanisms, and Disorders of Self-Domestication: Keys for Understanding Emotional and Social Communication from an Evolutionary Perspective

Molecules, Mechanisms, and Disorders of Self-Domestication: Keys for Understanding Emotional and Social Communication from an Evolutionary Perspective

Role of Microglial Cells in Alzheimer’s Disease Tau Propagation

Association of IL-1β, IL-1α and IL-10 single nucleotide polymorphisms with Mini-Mental State Examination and event-related potentials

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