Neurobiology Of Aging Research Articles

Emerging Trends and Hot Topics of Non-Invasive Electroencephalography Research in the Elderly: A Bibliometric Analysis from 2014 to 2023.

Electroencephalography (EEG) has been rapidly developed and is widely used in both clinical and scientific fields. Original studies on non-invasive EEG in the elderly have been of great importance owing to the global aging trend. The present study aimed to provide a bibliometric overview on current status and trends in this research field. We searched the Web of Science Core Collection for articles published during 2014 and 2023. Synonyms for EEG and the elderly were combined as a retrieval strategy. Invasive EEG and secondary studies were excluded. Online filters and manual reviews were applied to select eligible articles. Basic bibliometric parameters were analyzed and visualized using VOSviewer and Excel software. A total of 1656 publications were filtered, and 655 of which were finally included. In general, publication counts have steadily increased over the last 10 years. A sharp rise in publications occurred in 2021, and then remained at a high level. Authors and institutions from high-income countries/regions such as the United States of America (USA), China, and Germany were more productive and made significant contributions. Journals specialized in neuroscience, such as Frontiers in Aging Neuroscience, Neurobiology of Aging, and Clinical Neurophysiology, were popular among authors. Articles on aging, Alzheimer's disease (AD), mild cognitive impairment (MCI), dementia, memory, event-related potentials, attention, and the brain were more likely to use EEG. The newer topics included anesthesia, postoperative delirium (POD), confusion assessment method, connectivity, validation, and power. This bibliometric study provides fundamental knowledge on the current status and hot spots of the original studies on EEG in elderly, which is beneficial to researchers in paving future investigations of neuroscience and neural diseases.

Elevated Renal Oxidative Stress and Na+ Transporters are Associated with Hypertension in Postpartum Preeclamptic Rats

Background: Approximately 5-10% of US pregnancies result in preeclampsia (PE). PE is characterized by new onset hypertension (HTN) during pregnancy and is usually accompanied by end-organ damage, especially in the kidneys. Postpartum (PP) women and dams that had PE have an increased risk of developing HTN and chronic kidney disease (CKD) later in life. However, mechanisms linking PE to the long-term development of HTN and CKD are unknown. One aspect that may contribute to renal injury in PP PE women and dams is oxidative stress. Elevated concentrations of oxidative stress have been shown to augment the abundance and activity of renal transporters to increase sodium (Na+) reabsorption and blood volume. These alterations in renal transporters can consequently increase Na+ and water to facilitate HTN. Thus, we hypothesize that at 6 weeks PP (~3 human years), PE dams will display increased oxidative stress, renal Na+ transporter abundance, and elevated blood pressure (BP). Methods: Pregnant Sprague Dawley rats were randomly assigned to two groups: normal (CON) and PE dams. On gestational day 14, the reduced uterine perfusion pressure surgery was performed to mimic placental ischemia and generate a model of PE. Dams gave birth naturally and weaned for 3 weeks. After 6 weeks PP, BP was measured via carotid catheterization, and kidneys were removed and sectioned. Western blots were used to quantify renal Na+ transporters: Na+ K+ 2Cl− transporter (NKCC2) in the kidney medulla (KM) and epithelial Na+ channel (ENaC) in both the kidney cortex (KC) and KM. Oxidative stress was evaluated by heat shock protein 1 (HSP-1), copper zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) via Western blots. Hydrogen peroxide (H2O2) and antioxidant capacity concentrations were assessed via colorimetric assays. Results: PP PE dams had increased BP (126.3±6.18vs105.7±3.74 mmHg, p<0.05) at 6 weeks after birth. KC HSP-1, H2O2, MnSOD, and antioxidant capacity were unchanged between groups. However, KC CuZnSOD protein abundance was decreased in PP PE dams (69.51±11.64vs100±5.73 IU/Protein/Control%, p<0.05). In the KM, HSP-1 abundance (113.7±3.3vs100±5.07 IU/Protein/Control%, p=0.06) and H2O2 concentrations (1.97±0.11vs1.31± 0.38 nM H2O2/mg Protein, p=0.08) were elevated in PP PE dams. MnSOD, CuZnSOD, and antioxidant capacity were unchanged between groups in the KM. No changes occurred in KC and KM ENaC protein abundance. However, NKCC2 protein abundance was elevated by ~50% in PP PE dams (151.71±22.17vs100±5.59 IU/Protein/Control%, p=0.06). Conclusion: In summary, BP, oxidative stress, and NKCC2 were elevated in PP PE dams at 6 weeks. Perhaps, the presence of oxidative stress in the KM may lead to increased NKCC2 abundance. However, more studies are warranted to make this conclusion. NKCC2 elevation may result in increased Na+ and water reabsorption, leading to an increase in BP. Future studies will assess the role of renal oxidative stress to regulate Na+ transporters in PP PE dams and determine the timeline after birth (PP) in which changes in oxidative stress, Na+ transporters, and BP occur. In summary, this study is clinically relevant because it indicates that both oxidative stress and NKCC2 in the KM, separately or together, may have a formative role in the pathogenesis of HTN and CKD in PP PE women later in life. This research was supported by the Neurobiology of Aging and Alzheimer’s Disease Training Program (funded by NIH training grant T32 AG020494). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A bibliometric and visual analysis of epigenetic research publications for Alzheimer's disease (2013-2023).

Currently, the prevalence of Alzheimer's disease (AD) is progressively rising, particularly in developed nations. There is an escalating focus on the onset and progression of AD. A mounting body of research indicates that epigenetics significantly contributes to AD and holds substantial promise as a novel therapeutic target for its treatment. The objective of this article is to present the AD areas of research interest, comprehend the contextual framework of the subject research, and investigate the prospective direction for future research development. ln Web of Science Core Collection (WOSCC), we searched documents by specific subject terms and their corresponding free words. VOSviewer, CiteSpace and Scimago Graphica were used to perform statistical analysis on measurement metrics such as the number of published papers, national cooperative networks, publishing countries, institutions, authors, co-cited journals, keywords, and visualize networks of related content elements. We selected 1,530 articles from WOSCC from January 2013 to June 2023 about epigenetics of AD. Based on visual analysis, we could get that China and United States were the countries with the most research in this field. Bennett DA was the most contributed and prestigious scientist. The top 3 cited journals were Journal of Alzheimer's Disease, Neurobiology of Aging and Molecular Neurobiology. According to the analysis of keywords and the frequency of citations, ncRNAs, transcription factor, genome, histone modification, blood DNA methylation, acetylation, biomarkers were hot research directions in AD today. According to bibliometric analysis, epigenetic research in AD was a promising research direction, and epigenetics had the potential to be used as AD biomarkers and therapeutic targets.

Genome-wide association study in Alzheimer’s disease: a bibliometric and visualization analysis

BackgroundThousands of research studies concerning genome-wide association studies (GWAS) in Alzheimer’s disease (AD) have been published in the last decades. However, a comprehensive understanding of the current research status and future development trends of GWAS in AD have not been clearly shown. In this study, we tried to gain a systematic overview of GWAS in AD by bibliometric and visualization analysis.MethodsThe literature search terms are: (“genome-wide analysis” or “genome-wide association study” or “whole-genome analysis”) AND (“Alzheimer’s Disease” or “Alzheimer Disease”). Relevant publications were extracted from the Web of Science Core Collection (WoSCC) database. Collected data were further analyzed using VOSviewer, CiteSpace and R package Bibliometrix. The countries, institutions, authors and scholar collaborations were investigated. The co-citation analysis of publications was visualized. In addition, research hotspots and fronts were examined.ResultsA total of 1,350 publications with 59,818 citations were identified. The number of publications and citations presented a significant rising trend since 2013. The United States was the leading country with an overwhelming number of publications (775) and citations (42,237). The University of Washington and Harvard University were the most prolific institutions with 101 publications each. Bennett DA was the most influential researcher with the highest local H-index. Neurobiology of Aging was the journal with the highest number of publications. Aβ, tau, immunity, microglia and DNA methylation were research hotspots. Disease and causal variants were research fronts.ConclusionThe most frequently studied AD pathogenesis and research hotspots are (1) Aβ and tau, (2) immunity and microglia, with TREM2 as a potential immunotherapy target, and (3) DNA methylation. The research fronts are (1) looking for genetic similarities between AD and other neurological diseases and syndromes, and (2) searching for causal variants of AD. These hotspots suggest noteworthy directions for future studies on AD pathogenesis and genetics, in which basic research regarding immunity is promising for clinical conversion. The current under-researched directions are (1) GWAS in AD biomarkers based on large sample sizes, (2) studies of causal variants of AD, and (3) GWAS in AD based on non-European populations, which need to be strengthened in the future.

Neurobiology of Aging: New Insights From Across the Research Spectrum.

Neurobiology of Aging: New Insights From Across the Research Spectrum.

Corrigendum to “Does Late-life Depression Accelerate Aging?” [Am J Geriatr Psychiatry 31 (2023) 10–13

The editor regrets that the printed version of the above editorial commentary in the January, 2023 edition of AJGP) contained several errors. The correct and final version of the editorial commentary appears here. It offers a clear and robust discussion of the interface between geroscience and geriatric mental health and of the importance and innovation of the finding presented in the original research article. Does Late-Life Depression Accelerate Aging?The American Journal of Geriatric PsychiatryVol. 31Issue 1PreviewDepression in older adults occurs in the context of biological aging that contributes to the clinical symptoms, biomarkers, and the course of the disease.1 Neurobiology of aging and late-life mental disorders share features of increased cellular senescence, inflammation, and reduced mitochondrial function. In addition, serious mental disorders (SMDs), including major depression, are associated with an increased risk of medical illnesses and premature mortality from natural causes, with lifespans up to 25 years shorter than the general population, even after controlling for suicide. Full-Text PDF

Ovarian steroid hormones: A long overlooked but critical contributor to brain aging and Alzheimer's disease.

Ovarian hormones, particularly 17β-estradiol, are involved in numerous neurophysiological and neurochemical processes, including those subserving cognitive function. Estradiol plays a key role in the neurobiology of aging, in part due to extensive interconnectivity of the neural and endocrine system. This aspect of aging is fundamental for women’s brains as all women experience a drop in circulating estradiol levels in midlife, after menopause. Given the importance of estradiol for brain function, it is not surprising that up to 80% of peri-menopausal and post-menopausal women report neurological symptoms including changes in thermoregulation (vasomotor symptoms), mood, sleep, and cognitive performance. Preclinical evidence for neuroprotective effects of 17β-estradiol also indicate associations between menopause, cognitive aging, and Alzheimer’s disease (AD), the most common cause of dementia affecting nearly twice more women than men. Brain imaging studies demonstrated that middle-aged women exhibit increased indicators of AD endophenotype as compared to men of the same age, with onset in perimenopause. Herein, we take a translational approach to illustrate the contribution of ovarian hormones in maintaining cognition in women, with evidence implicating menopause-related declines in 17β-estradiol in cognitive aging and AD risk. We will review research focused on the role of endogenous and exogenous estrogen exposure as a key underlying mechanism to neuropathological aging in women, with a focus on whether brain structure, function and neurochemistry respond to hormone treatment. While still in development, this research area offers a new sex-based perspective on brain aging and risk of AD, while also highlighting an urgent need for better integration between neurology, psychiatry, and women’s health practices.

An investigation of HCV as a predictor of cognitive decline: The Bio‐Hermes protocol

AbstractBackgroundA 2018 NIA‐AA Research Framework extended the biological definition of Alzheimer’s disease (AD) from biomarkers of amyloid (A) and tau (T) to include measures of neurodegeneration (N) thus enabling more detailed staging and identification of participants potentially closest to clinical decline (N+) (AlzheimersDement.2018;14(4):535‐562). This framework is only partially implemented in clinical trials as N is rarely considered a selection criterion. Hippocampal volume (HCV) measured from magnetic resonance imaging (MRI) has been proposed as a widely available, robust tool to define N+ (AlzheimersDement.2014;10(4):421‐429.e3).MethodParticipant selection through N+ will be validated in a sub‐study of the Bio‐Hermes trial planned by the Global Alzheimer’s Platform Foundation®. The Bio‐Hermes trial will assess biomarkers of Aβ, phospho‐tau, and neurofilament light in approximately 1,000 participants in three cohorts: cognitively normal, mild cognitive impairment, probable AD. A baseline MRI will be performed in approximately 200 additional participants randomized in a substudy. A pre‐defined HCV cut‐off from the Learning Embeddings for Atlas Propagation (LEAP) algorithm was identified to define N+ status (NeuroImage.2010;49(2):1316‐1325). The sub‐study will enrol participants willing to forgo treatment studies for 12 months to allow standardized measures of progression. Correlation with clinical measures and clinical decline will be compared in N+ and N‐ populations in the three cohorts to validate the benefit of full ATN staging in trial design.ResultWhile most publications using the LEAP algorithm for N+ AD patient stratification define N+ cut‐offs based on HCV percentiles in the analysed dataset (Neurobiology of Aging. 2012;33:2272–2281, Neurology. 2013;80(12):1124‐1132, , Neurology. 2016; 87(12):1235–124, Alzheimers Dement. 2018;14(7):1076, Alzheimers Dement. 2020; 10.1002/alz.037912), one study deployed percentiles from a healthy reference cohort (Neurobiology of Aging. 2014;35:808‐818). Based on prior work and simulations of the Bio‐Hermes trial cohorts, the N+ cut‐off was set at HCV=5.4cm3.ConclusionThe presented study design validates the use of MRI as inclusion criterion in AD clinical trials to fully implement ATN staging. As MRI is a standard tool during screening for AD clinical trials, additional participant characterisation can be achieved at minimal extra cost and burden, significantly improving trial power.

Clinical profile of an Alzheimer´s disease cohort in the Peruvian population

AbstractBackgroundAmong older Peruvians (over 65‐years) the prevalence of dementia is 7%, with 56% meeting clinical criteria for Alzheimer Disease (AD). Peruvians, are an admixed population with approximately 80% Amerindian ancestral background. We have ascertained a cohort of Alzheimer Disease (AD) cases and cognitively intact controls for genetic studies.MethodAll participants have been recruited since 2019 using community outreach ascertainment strategies and hospital‐based recruitment from Lima, Peru. Cases were assessed by neurologist following NINDS/ADRDA criteria; and completed a comprehensive neurocognitive, neuropsychiatric and functional assessments. Controls were screened using MMSE, Clock drawing test and Pfeffer functional activities questionnaire. IRBs approvals from the participating Peruvian institutions and University of Miami were obtained for this study.ResultA total of 102 AD cases (4 familial cases) and 152 controls were recruited since 2019 to December 2020. For AD cases: age at examination were 76.5±9.09, age at onset were 72.15±8.82, and 63.7% were female, average of 9.9±4.9 year of education. For controls: age at examination were 73.13±6.54, 62.5% were female, average of 11.62±4.41 year of education. Among cases diagnosis was classified as: 62.8% possible AD (two cases screened for Cerebrospinal fluid Abeta42 and tau protein levels) and 37.2% probable AD. Clinical and cognitive assessment profile for cases: MMSE average score was 17.2± 4.9 and Addenbrook’s Cognitive Examination average score was 38.5± 21.7 with memory loss predominance. Based on NPI the most frequent neuropsychiatric symptoms were irritability (51%), delusions (46%) and apathy (45%). Severity of dementia were assessed by CDR (CDR=3 for 33.9%, CDR=2 for 32.3%, CDR=1 for 24.2% and CDR=0.5 for 9.7%). Depressive symptoms were assessed with Geriatric Depression Scale with an average of 4.4±3.5 .ConclusionThe clinical features of the AD cohort in the Peruvian population are consistent with previous reports. There is a tendency of a higher level of education in the control . Among the Peruvian AD cohort, the main neuropsychiatric symptoms are irritability, delusions and apathy consistent with the predominance of moderate to severe dementia. Reference: Marca V. et al. Dissecting the role of Amerindian genetic ancestry and ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population, Neurobiology of Aging, 2020.

A Canadian cohort with the IVS10+14 MAPT mutation

AbstractBackgroundThe IVS10+14 microtubule‐associated protein tau gene (MAPT) mutation causes dysregulated protein splicing of MAPT, resulting in abnormal 4‐repeat isoform tau accumulation and associated with neurodegeneration. Three families expressing the IVS10+14 MAPT mutation have been reported who express the IVS10+14 MAPT mutation displaying a high degree of interfamilial heterogeneity in their clinical presentation. Herein, we describe the clinical and neuropathological presentation of a new Canadian cohort with this mutation.MethodClinical and neuropathological records, including neuropsychological and cognitive assessments, and stained neuropathological sections, were obtained for three family members with the IVS10+14 MAPT mutation. The records were reviewed and compared to previously reported families with this mutation.ResultThe Canadian cohort displayed many of the symptoms previously described in cases with the IVS10+14 MAPT mutation, including prominent motor, cognitive, behavioural, and behavioural symptoms. Additionally, consistent with the interfamilial heterogeneity described in literature, our cohort exhibited profound sensory and sleep abnormalities. Neuropathological information was available for two cases, in which one had widespread cortical and subcortical tau deposition and atrophy, while neuropathological changes in the other case was milder with the exception substantia nigral atrophy.ConclusionOur cohort demonstrate that while the IVS10+14 MAPT mutation often results in motor, cognitive and behavioural clinical features, sensory and sleep abnormalities are also manifestations of the mutation. Clinicopathological correlations were able to explain symptom presence and severity for two of the three examined cases. This underlines the need to explore alternate mechanisms and metrics of brain dysfunction in tauopathy in addition to tau burden and neuronal loss. Reference: Maxwell SP, Cash MK, Rockwood K, Fisk JD, Darvesh S. 2021. Clinical and Neuropathological Variability in the Rare IVS10+14 Tau Mutation. Neurobiology of Aging. In Press. DOI: 10.1016/j.neurobiolaging.2021.01.004.

Dignity of Older Persons With Mental Health Conditions: Why Should Clinicians Care?

With a steady increase in population aging, the proportion of older people living with mental illness is on rise. This has a significant impact on their autonomy, rights, quality of life and functionality. The biomedical approach to mental healthcare has undergone a paradigm shift over the recent years to become more inclusive and rights-based. Dignity comprises of independence, social inclusion, justice, equality, respect and recognition of one's identity. It has both subjective and objective components and influences life-satisfaction, treatment response as well as compliance. The multi-dimensional framework of dignity forms the central anchor to person-centered mental healthcare for older adults. Mental health professionals are uniquely positioned to incorporate the strategies to promote dignity in their clinical care and research as well as advocate for related social/health policies based on a human rights approach. However, notwithstanding the growing body of research on the neurobiology of aging and old age mental health disorders, dignity-based mental healthcare is considered to be an abstract and hypothetical identity, often neglected in clinical practice. In this paper, we highlight the various components of dignity in older people, the impact of ageism and mental health interventions based on dignity, rights, respect, and equality (including dignity therapy). It hopes to serve as a framework for clinicians to incorporate dignity as a principle in mental health service delivery and research related to older people.

P.014 A Novel Canadian Family with the Rare IVS10+14 Tau Mutation

Background: The IVS10+14 mutation in the microtubule-associated protein tau gene, MAPT, is a rare point mutation that dysregulates tau splicing resulting in pathological aggregation. This mutation has been identified in three families with severe neurodegenerative disease. We characterized the clinicopathological features of a fourth, Canadian family with the IVS10+14 MAPT mutation and compared them to previously reported families. Methods: Clinical and neuropathological records from three family members with the IVS10+14 MAPT mutation were reviewed. Neuropathological section from one available case were analyzed. Results: Considerable interfamilial phenotypic heterogeneity is reported in all cohorts that express the IVS10+14 MAPT mutation, with prominent motor, cognitive, behavioural, and respiratory symptoms. The Canadian cohort also expressed profound sensory and sleep abnormalities, not reported previously. In the two siblings with available neuropathological records, neuropathological changes ranged from mild to severe. Conclusions: All families expressing the IVS10+14 MAPT mutation display striking inter- and intrafamilial clinical and neuropathologic phenotypic variability. Our cohort adds sensory and sleep abnormalities as potential symptoms and illustrates a lack of clear clinicopathological correlates for these heterogenous symptoms. Reference: Maxwell et al. 2021. Clinical and Neuropathological Variability in the Rare IVS10+14 Tau Mutation. Neurobiology of Aging. In Press. DOI: 10.1016/j.neurobiolaging.2021.01.004.

A Neuroscience Primer for Integrating Geroscience With the Neurobiology of Aging.

Neuroscience has a rich history of studies focusing on neurobiology of aging. However, much of the aging studies in neuroscience occur outside of the gerosciences. The goal of this primer is 2-fold: first, to briefly highlight some of the history of aging neurobiology and second, to introduce to geroscientists the broad spectrum of methodological approaches neuroscientists use to study the neurobiology of aging. This primer is accompanied by a corresponding geroscience primer, as well as a perspective on the current challenges and triumphs of the current divide across these 2 fields. This series of manuscripts is intended to foster enhanced collaborations between neuroscientists and geroscientists with the intent of strengthening the field of cognitive aging through inclusion of parameters from both areas of expertise.

Age- and cognition-related differences in the gray matter volume of the chimpanzee brain (Pan troglodytes): A voxel-based morphometry and conjunction analysis.

Several primate species have been shown to exhibit age-related changes in cognition, brain, and behavior. However, severe neurodegenerative illnesses, such as Alzheimer's disease (AD), were once thought to be uniquely human. Recently, some chimpanzees naturally were documented to develop both neurofibrillary tangles and amyloid plaques, the main characteristics of AD pathology. In addition, like humans and other primates, chimpanzees show similar declines in cognition and motor function with age. Here, we used voxel-based morphometry to examine the relationships among gray matter volume, age, and cognition using magnetic resonance imaging scans previously acquired from chimpanzees (N = 216). We first determined the relationship between age and gray matter volume, identifying the regions that declined with age. With a subset of our sample (N = 103), we also determined differences in gray matter volume between older chimpanzees with higher cognition scores than expected for their age, and older chimpanzees with lower than expected scores. Finally, we ran a conjunction analysis to determine any overlap in brain regions between these two analyses. We found that as chimpanzees age, they lose gray matter in regions associated with cognition. In addition, cognitively healthy older chimpanzees (those performing better for their age) have greater gray matter volume in many brain regions compared with chimpanzees who underperform for their age. Finally, the conjunction analysis revealed that regions of age-related decline overlap with the regions that differ between cognitively healthy chimpanzees and those who underperform. This study provides further evidence that chimpanzees are an important model for research on the neurobiology of aging. Future studies should investigate the effects of cognitive stimulation on both cognitive performance and brain structure in aging nonhuman primates.

Brain biomarkers and cognition across adulthood.

Understanding the associations between brain biomarkers (BMs) and cognition across age is of paramount importance. Five hundred and sixty-two participants (19-80 years old, 16 mean years of education) were studied. Data from structural T1, diffusion tensor imaging, fluid-attenuated inversion recovery, and resting-state functional magnetic resonance imaging scans combined with a neuropsychological evaluation were used. More specifically, the measures of cortical, entorhinal, and parahippocampal thickness, hippocampal and striatal volume, default-mode network and fronto-parietal control network, fractional anisotropy (FA), and white matter hyperintensity (WMH) were assessed. z-Scores for three cognitive domains measuring episodic memory, executive function, and speed of processing were computed. Multiple linear regressions and interaction effects between each of the BMs and age on cognition were examined. Adjustments were made for age, sex, education, intracranial volume, and then, further, for general cognition and motion. BMs were significantly associated with cognition. Across the adult lifespan, slow speed was associated with low striatal volume, low FA, and high WMH burden. Poor executive function was associated with low FA, while poor memory was associated with high WMH burden. After adjustments, results were significant for the associations: speed-FA and WMH, memory-entorhinal thickness. There was also a significant interaction between hippocampal volume and age in memory. In age-stratified analyses, the most significant associations for the young group occurred between FA and executive function, WMH, and memory, while for the old group, between entorhinal thickness and speed, and WMH and speed, executive function. Unique sets of BMs can explain variation in specific cognitive domains across adulthood. Such results provide essential information about the neurobiology of aging.

Melody Processing Characterizes Functional Neuroanatomy in the Aging Brain.

The functional neuroanatomical mechanisms underpinning cognition in the normal older brain remain poorly defined, but have important implications for understanding the neurobiology of aging and the impact of neurodegenerative diseases. Auditory processing is an attractive model system for addressing these issues. Here, we used fMRI of melody processing to investigate auditory pattern processing in normal older individuals. We manipulated the temporal (rhythmic) structure and familiarity of melodies in a passive listening, ‘sparse’ fMRI protocol. A distributed cortico-subcortical network was activated by auditory stimulation compared with silence; and within this network, we identified separable signatures of anisochrony processing in bilateral posterior superior temporal lobes; melodic familiarity in bilateral anterior temporal and inferior frontal cortices; and melodic novelty in bilateral temporal and left parietal cortices. Left planum temporale emerged as a ‘hub’ region functionally partitioned for processing different melody dimensions. Activation of Heschl’s gyrus by auditory stimulation correlated with the integrity of underlying cortical tissue architecture, measured using multi-parameter mapping. Our findings delineate neural substrates for analyzing perceptual and semantic properties of melodies in normal aging. Melody (auditory pattern) processing may be a useful candidate paradigm for assessing cerebral networks in the older brain and potentially, in neurodegenerative diseases of later life.

Crystal Structure of Carbonic Anhydrase II in Complex with an Activating Ligand: Implications in Neuronal Function.

Carbonic anhydrase (CA) plays a key role in neuronal signaling, providing bicarbonate and proton ions for GABAergic and glutamatergic neuronal function. Activation of CA isoforms expressed in neurons have been shown to have implications in the prognosis of Alzheimer's disease and dementia, while inhibitors of CAs are clinically used in the treatment of epilepsy, emphasizing the importance of this family of enzymes in both disease and normal neuronal function. Previously, compounds have been reported to enhance activity of CAs in an aging rat model, but their mechanism of action was not known. We report the 1.6Å resolution structure of an imidazole-based CA activator in complex with the ubiquitously-expressed human CA II. Based on the structure, a proposed mechanism of CA activation by the compound and its potential applications in the neurobiology of aging are discussed.

Investigate the effect of HD-tDCS on the prefrontal cortex using fNIRS for neurorehabilitation

Investigate the effect of HD-tDCS on the prefrontal cortex using fNIRS for neurorehabilitation

Keynote speakers

Mutually-inversistic machine learning is based on inverse hypothetical inference of mutually-inversistic logic constructed by the author. In mutually-inversistic logic, there are 8 kind of hypothetical inferences, all of which are from the major premise and the minor premise to infer the conclusion. For each hypothetical inference, there are 2 inverse hypothetical inferences, one is from the minor premise and the conclusion to the major premise, the other is from the major premise and the conclusion to the minor premise. Therefore, there are 16 kind of mutually-inversistic machine learning models altogether. FOIL, decision tree learning in inductive learning, rough set learning, genetic algorithm, inverse resolution in inductive logic programming are special cases of mutually-inversistic machine learning.

In vivo characterization of different alpha-synuclein variants

Event Abstract Back to Event In vivo characterization of different alpha-synuclein variants Anke Van Der Perren1*, Géraldine Gelders1, Nikol Shakhbazyan1, Francesca Macchi1, Chris Van Den Haute1, 2 and Veerle Baekelandt1, 2 1 KU Leuven, Neurosciences, Belgium 2 KU Leuven, Belgium Alpha-synuclein (α-SYN) is a key player in Parkinson’s disease, but the exact relationship between α-SYN aggregation and the pathogenesis remains unresolved. There is emerging evidence that α-SYN can adopt distinct conformations that are characterized by noticeable differences in structural and phenotypic features (Peelaerts et al. Nature, 2015). In addition, it has been shown that neuroinflammatory processes are closely linked to dopaminergic neurodegeneration. We presume that immune alterations in response to different α-SYN conformations may play a critical role in modulating the progression as well as the outcome of the disease. In this study, we aim to analyze the effect of different α-SYN mutants (different propensity to form oligomeric or fibrillar aggregates) in terms of aggregation, neurodegeneration and neuroinflammation in vivo. More specifically, we will compare the aggregation prone A53T clinical mutant which we have previously characterized in detail (Van der Perren et al. Neurobiology of aging, 2014, 2015) with WT α-SYN, the 1-110 truncation promoting α-SYN aggregation and the artificial E57K, E35K and A56P α-SYN mutants that were shown to induce oligomers but not fibrils. We overexpressed the different α-SYN mutants in the substantia nigra (SN) of the rat using rAAV2/7 viral vectors. To assess motor deficits the rats were subjected to the cylinder test. Two and four weeks post injection a significant difference was observed in the use of the left forepaw between the groups with the 1-110 truncation and the oligomeric mutants (E57K, E35K, A56P). Thioflavin S staining and oligomer-specific antibodies were used to discern fibrillar and oligomeric α-SYN as well as biochemical analysis using sarkosyl treatment. The level of neurodegeneration was assessed in the SN and the striatum by immunohistochemical staining. This revealed clear differences between fibrillary and oligomeric α-SYN. Characterization of neuroinflammatory markers is ongoing. These results support our hypothesis that distinct α-SYN conformations may play a critical role in the progression of Parkinson’s disease. Keywords: alpha-Synuclein, Parkinson’s disease, neurodegeneration, Neuroinflammation, vector-based model Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Poster Presentation Topic: Disorders of the Nervous System Citation: Van Der Perren A, Gelders G, Shakhbazyan N, Macchi F, Van Den Haute C and Baekelandt V (2019). In vivo characterization of different alpha-synuclein variants. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00052 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Apr 2017; Published Online: 25 Jan 2019. * Correspondence: Dr. Anke Van Der Perren, KU Leuven, Neurosciences, Leuven, Vlaams-Brabant, 3000, Belgium, anke.vanderperren@kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anke Van Der Perren Géraldine Gelders Nikol Shakhbazyan Francesca Macchi Chris Van Den Haute Veerle Baekelandt Google Anke Van Der Perren Géraldine Gelders Nikol Shakhbazyan Francesca Macchi Chris Van Den Haute Veerle Baekelandt Google Scholar Anke Van Der Perren Géraldine Gelders Nikol Shakhbazyan Francesca Macchi Chris Van Den Haute Veerle Baekelandt PubMed Anke Van Der Perren Géraldine Gelders Nikol Shakhbazyan Francesca Macchi Chris Van Den Haute Veerle Baekelandt Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.