Displaying One Session

POSTER SESSION
Session Type
POSTER SESSION
Room
EXHIBITION HALL
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM

TRANSLATIONAL POTENTIAL OF TWO ETIOLOGICALLY RELEVANT RAT MODELS OF NEUROCOGNITIVE DISORDERS: BEHAVIORAL, HISTOPATHOLOGICAL AND MOLECULAR ASPECTS

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

Preclinical animal models play crucial role in the understanding of neurodegeneration, and in the identification of new biomarkers and novel pharmacological targets for neurocognitive disorders (NCDs). The aim of our study was to assess the translational potential of two different animal models of NCDs in functional, histopathological and molecular aspects.

Methods

Two different rat models of cognitive impairment were established: a model of repetitive mild traumatic brain injuries (rmTBI), and a natural aging model. A broad spectrum of cognitive domains were measured: episodic memory in the novel object recognition test (NOR), spatial memory in the Morris water maze (MWM) task, and sustained-attention in the psychomotor vigilance task (PVT). Histopathological changes were assessed using immunohistochemical methods. Furthermore, brain and serum samples were analyzed using qPCR and ELISA to identify biochemical indicators of neurodegeneration and neuroinflammation.

Results

Rats subjected to rmTBI showed significant deficits in NOR and MWM without expressing elevated levels of classical TBI biomarkers (APP, GFAP). In the aging model, 24+ months old rats performed worse in the NOR, MWM and PVT compared to young controls, and increased number of activated microglia, and decreased RNA- and protein-expression of BDNF was found in their brain.

Conclusions

Our results confirmed that the rmTBI and aging models offer promising alternatives to other dementia models commonly used in pharmacology (e.g., the scopolamine-induced transient amnesia model). Since the aging model includes both mechanisms (neuroinflammation and neurodegeneration) and cognitive symptoms seen in NCDs, it provides an excellent model for further preclinical translational pharmacology research.

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ALZPED: A NEW DATA RESOURCE FOR IMPROVING THE RIGOR, REPRODUCIBILITY, TRANSPARENCY AND TRANSLATION OF ALZHEIMER'S DISEASE PRECLINICAL RESEARCH.

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

A major challenge to successful development of therapies for Alzheimer’s disease (AD) is poor translation of preclinical efficacy from animal models to the clinic. Key contributing factors to the poor translation include poor reproducibility of published data, lack of rigor in study design and methodology. To address these issues the National Institute on Aging has created AlzPED, a publicly available database designed as a searchable knowledge platform for sharing and mining of experimental details, designs, data and methods relating to preclinical testing of candidate therapeutics in AD animal models.

Methods

Using key word-driven literature searches published studies are acquired and curated for data on authors, funding source, AD animal models, therapeutic targets and agents, study design, and outcome measures.

Results

AlzPED currently houses curated summaries from over 900 published studies. Summaries are searchable by author, funding source, animal model, therapeutic target and therapeutic agent and elements of experimental rigor and design. At present, the database contains data on 180 animal models, 168 therapeutic targets, 803 therapeutic agents and, more than 1500 AD-related outcome measures.

Conclusions

Analysis of curated studies demonstrates serious deficiencies in reporting critical elements of methodology such as power calculation, blinding for treatment/outcomes, randomization, sex of animal used and balancing for sex, animal genetic background and others. These deficiencies diminish the scientific rigor, reproducibility and translational value of the preclinical studies. Thus, it is evident that a standardized set of best practices is required for successful translation of therapeutic efficacy in AD research.

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GLIA TREATED WITH PARTICULATE MATTER INCREASE NEURONAL INJURY THROUGH PAI-1 ACTIVATION

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

Particulate matter 2.5 (PM2.5) can gain access to the lungs and the circulatory system and may sequentially cross the blood brain barrier (BBB). Recent data suggested that these particles reaching the brain may cause neurological disorders including AD and PD. However, the precise mechanisms by which PM2.5 contributed to neuronal damage have not been clarified. And, there is no study on how to prevent PM2.5-induced inflammation and neurotoxicity. In this study, we have demonstrated that PM2.5 increases the PAI-1 activity and neuroinflammation, and that natural compounds such as astaxanthin and Egb761 can prevent the subsequent neurotoxicity, mainly based on its anti-oxidative and anti-inflammatory properties.

Methods

In this regard, we examined 1) the mRNA expression of inflammatory mediators including iNOS, IL-1b, tPA, PAI-1, TNFa, c1q, TGFb and BDNF, 2) nitric oxide and reactive oxygen species production, 3) tPA and PAI-1 activity, and 4) neurite extension assay using the immunocytochemistry. We used a well-characterized Diesel particulate matter, PM2.5, from SIGMA-Aldrich.

Results

PM2.5 increased inflammatory cytokines such as IL-6 production in rat astrocytes, and PAI-1 mRNA expression activity in rat primary astrocytes. Astaxanthin and Egb761 attenuated PM2.5-induced increased ROS and other inflammatory cytokines expressions and prevented neuronal cell death in rat primary cortical neurons.

Conclusions

Our results show that PM2.5 activates the astrocytes through PAI-1 activation leading to neurotoxicity, and astaxanthin and Egb761 can prevent this through the inhibition of astrocytes activation. These results demonstrate that the potential beneficial effects of astaxanthin and Egb761 against air pollution exposure such as PM2.5.

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LASTING IMPROVEMENT OF ASSOCIATIVE MEMORY AND ALTERED BRAIN ACTIVITY IN OLDER ADULTS THROUGH REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS)

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM
Presenter

Abstract

Aims

Cognitive decline is part of normal aging accompanied by alterations of large-scale brain connectivity supporting high-level cognition. Associative memory is one of the cognitive domains most vulnerable to aging. The dorsolateral prefrontal cortex (DLPFC) is critically involved in associative memory and other core cognitive processes, and it is accessible by repetitive transcranial magnetic stimulation (rTMS). Given that studies using rTMS to improve associative memory along with altered brain plasticity in healthy older adults have been lacking, we applied rTMS to the right DLPFC of normal older adults in a double-blind design with well-matched experimental and sham groups.

Methods

Both groups participated in active rTMS or sham stimulation for two weeks. There were 10 daily stimulation sessions, with 5 sessions in each week. All participants completed a battery of neuropsychological tests and MRI scanning individually at the pre-intervention (baseline) and post-intervention assessment (post-test).

Results

Multiple-session rTMS on right DLPFC improved associative memory performance and concomitantly altered localized spontaneous brain activity. The altered functional plasticity changes significantly contributed to associative memory improvement. Importantly, the cognitive enhancement persisted six months after the brain stimulation.

Conclusions

These findings indicate that targeted rTMS can modulate functional plasticity to improve cognition in the aging brain.

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MORBIDITY/MORTALITY PARADOX AND IMPACT OF ISOLATION ON THE BEHAVIORAL PHENOTYPE OF OLD MALE AND FEMALE MICE WITH NORMAL AGING AND ALZHEIMER’S DISEASE.

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

Experimental gerontologists highlight the relevance of using aged animals to mimic the heterogeneity and complexity of the physiological aging process in humans, as well as the contribution of age on the symptomatic and mechanistic features of neurodegenerative processes. Similarly, gender medicine warns about the relevance of studying diseases under a sex- and gender-perspective. On the other hand, dementia is associated with increased mortality in comparison with aged control populations and according to the morbidity/mortality paradox, females show greater survival than males in spite of their worse neuropathological status. Similarly, translational research using old and very old animals has to overcome the sparsity of studies and confronts methodological difficulties due to natural constrains of aged animals and the ‘survivors bias’. We have addressed these questions in male and female 3xTg-AD mice for Alzheimer’s disease, where we describe such a mortality bias also exists.

Methods

The impact of social isolation on the behavioral and functional phenotype was then investigated in old (12- 16 and 19-month-old) animals modeling advanced stages and compared to age- and sex-matched non-transgenic counterparts with normal aging.

Results

Isolated animals showed worse cognitive function and increased BPSD-like symptoms, especially those related to neophobia and anxiety-like behaviors, with distinct patterns according to sex. However, these differences became less distinctive in the oldest age group of mice.

Conclusions

The results point at the relevance to take into consideration the social x age x sex interactions as they can define distinct genotype experimental scenarios and have an impact determining the behavioral output of preventive/therapeutical strategies.

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IMPACT OF OBSTRUCTIVE SLEEP APNEA IN THE COGNITIVE EVOLUTION OF ALZHEIMER’S DISEASE PATIENTS

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

To investigate the effect of OSA on the cognitive evolution of patients with AD.

Methods

In this prospective, single-center study (NCT02814045), patients with mild-moderate AD with and without untreated OSA were evaluated at the baseline and after 12, 24 and 36 months of follow-up. OSA was defined as an apnea-hypopnea index (AHI) >15/h. The primary outcome was measured by the cognitive scores on the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE).

Results

The cohort included 146 patients with 125 validated PSGs, from which 40 patients were diagnosed as non-OSA (32%) and 85 as OSA (68%). The median [IQR] age of the eligible individuals was 75.0 [72.0;80.0] years and the majority was composed of women (57.25%). In addition, the mean (SD) MMSE score at the baseline was 23.53 (2.23).

In the ADAS-cog score, the mean (SD) change at the 12 months of follow-up was 2.97 (5.73) and 0.29 (5.65) for the non-OSA and OSA group, respectively. The estimated mean (95%) difference between the groups was -2.76 (0.12 to 0.16) (p=0.033). No cognitive changes were observed at several cognitive domains evaluated. There was a cognitive decline along the 3 years of follow-up according to the MMSE score (p<0.001) (Figure 1), but no differences between the groups were observed.figure 1_page-0001.jpg

Conclusions

OSA was not associated with a worse cognitive evolution after 36 months of follow-up. Further studies will be necessary to improve the understanding of the OSA impact on the cognitive evolution of AD patients.

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SERUM URIC ACID, ALZHEIMER-RELATED BRAIN CHANGES, AND COGNITIVE IMPAIRMENT

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

Despite known associations of serum uric acid (UA) with Alzheimer’s disease (AD) dementia or cognitive impairment, the underlying neuropathological links were poorly understood. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Ab) and tau deposition, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensities (WMH). We also investigated the association between serum UA and cognitive performance, and then assessed whether such an association is mediated by the brain pathologies.

Methods

A total of 430 non-demented older adults underwent comprehensive clinical assessments, measurement of serum UA level, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging scans. Mini-Mental State Examination (MMSE) and word list recall (WLR) test scores were used to measure cognitive performance.

Results

Serum UA level was significantly associated with AD-CM, but not with Ab deposition, tau deposition, or WMH volume. Serum UA levels also had significant association with WLR and marginal association with MMSE; such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a mediating effect.

Conclusions

Higher serum UA may protect against AD-related cognitive decline by preserving AD-related regional brain metabolism.

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SOCIAL ISOLATION IMPACTS SOCIO-COGNITIVE ALZHEIMER'S DISEASE PHENOTYPE IN APP/PS1 MICE

Session Name
Β-AMYLOID DISEASES: ALZHEIMER´S DISEASE (AD), PRODROMAL AD, CEREBRAL AMYLOID ANGIOPATHY (CAA), DOWN SYNDROME (DS) & MILD COGNITIVE IMPAIRMENT (MCI) / TRANSLATIONAL ASPECTS / A7.ATRANSLATIONAL ASPECTS
Session Type
POSTER SESSION
Date
02.04.2020, Thursday
Session Time
10:00 AM - 07:00 PM
Room
EXHIBITION HALL
Lecture Time
10:00 AM - 10:00 AM

Abstract

Aims

In January 2018, Britain was the first in the world to adopt a Minister of Loneliness. This illustrates the changing view on loneliness: being lonely is not just a feeling of a lack of companionship, but also a serious health problem. Research has shown that lonely people express higher levels of cortical amyloid, an important marker of Alzheimer’s Disease (AD). Together with other studies a link between loneliness, (perceived) social isolation and AD is now undeniable, but it is hard to tell from human studies whether it is the cause or the effect of AD.

Methods

In an effort to study how social isolation and AD interact, we used APP/PS1 mice bearing human transgenes known to cause AD, and isolated them during adulthood in order to mimic loneliness in late-life. We looked at the effects of isolation on the behaviour and symptomatology typically present in AD patients by using a specific behavioural test battery to tap cognition, sociability, exploration and emotionality.

Results

Social isolation had distinct effects on the AD-related anxiogenic and dementia-like phenotype, it exacerbated social recognition memory deficits and even induced it in adult WT animals. After intense resocialization, this socio-cognitive deficit could be rescued in WT mice by increasing hippocampal neurogenesis, AD mice data are underway.

Conclusions

This sheds new light on the link between social isolation and dementia. We can conclude that social isolation is a risk factor for AD but it is a modifiable one. Targeting isolated individuals may therefore have the potential to decrease AD in the population.

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