Welcome to the AD/PD™ 2022 Interactive Program

The conference will officially run on Central European Time (CET) - Barcelona Time

To convert the conference times to your local time Click Here



 

633 Presentations

Sort By Relevance

PRE-RECORDED: TACKLING NEURODEGENERATIVE DISEASES: USING SYNERGIES ACROSS DISEASE AREAS TO SPEED DRUG DEVELOPMENT FOR PATIENTS

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 112
Lecture Time
09:40 AM - 09:55 AM

Abstract

Abstract Body

Objective: Neurodegenerative diseases share certain features: they are often characterized by accumulation of abnormal, toxic proteins; they have long prodromal periods; their clinical onset is often enabled and/or accelerated by aging. On the other hand, they differ in many important ways, including inheritance patterns; clinical symptoms --reflecting selective vulnerability of cell types and/or networks; and the time course by which they impair the nervous system. This discussion reviews how the evolution of drug development has benefitted from influences and learnings across different disease areas.

Methods: Congress-invited reflection on internal and external efforts to develop new treatments for Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.

Results: Drug development is beginning to leverage the similarities and accommodate the differences across these neurodegenerative diseases. We are targeting Alzheimer’s disease, Parkinson’s disease and Huntington’s disease with treatments that have overlapping mechanisms of action. The clinical development programs for all of these diseases are segmented according to stages, beginning with asymptomatic stages and including prodromal stages to define desirable populations in which to intervene. In addition, research tools, including biomarkers and sensitive digital outcome measures, are being developed on the bases of shared technologies.

Conclusion: Successful leveraging of learnings from one disease to another are expected to speed drug development for all.

Hide

SEX AND GENDER CONSIDERATIONS IN NEURODEGENERATIVE DISEASES: SCIENTIFIC EVIDENCE, BIASES, AND OPPORTUNITIES FOR PRECISION MEDICINE

Session Type
SYMPOSIUM
Date
Sun, 20.03.2022
Session Time
11:35 AM - 01:35 PM
Room
ONSITE: 113
Lecture Time
12:05 PM - 12:20 PM

Abstract

Abstract Body

Cumulating evidence has indicated high degree of patient variability in neurodegenerative disorders. Precision medicine, as already in use in oncology, might provide substantial progress in the field, from molecular diagnosis to tailored treatments.

In this regard, sex and gender differences are emerging as leading features driving patient heterogeneity in a variety of brain diseases, including Alzheimer. These differences offer therefore a useful starting point to discuss potential applications of precision medicine in neurology.
Taking the example of Alzheimer’s and Parkinson Disease, in this talk I will discuss the role of sex and gender differences in biomarker research, clinical trial design and development of digital health technologies, highlighting the work that the non-profit organization Women's Brain Project is doing in this field.

A proper understanding of sex and gender-differences will be key towards a precision medicine paradigm for neurodegenerative diseases, beyond a ‘one size fits all’ approach and towards sustainability.

Hide

BIOMARKER PREDICTION OF CLINICAL ONSET: INSIGHTS FROM FAMILIAL ALZHEIMER’S DISEASE

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE PLENARY: 115-117
Lecture Time
05:30 PM - 05:45 PM

Abstract

Abstract Body

There is increasing interest in conducting disease-modification trials in the presymptomatic stage of AD- when there is the greatest potential to save cognitive function and better chances of slowing progression.

Presymptomatic trials rely on recruiting individuals on a course towards symptomatic disease. The ability to stage participants is important for the selection of those most likely to benefit and to reduce heterogeneity and improve power.

Familial Alzheimer’s disease (FAD) caused by APP or PSEN mutations genes offer a means of studying presymptomatic disease and understanding the sequence of biomarker changes that may help predict where an individual is in on the disease trajectory and how far they are from symptom onset.

I will review the insights from presymptomatic FAD studies about the timing of fluid (CSF, blood) biomarker changes relative to symptom onset and discuss their relevance to sporadic and familial AD. I will describe the special case of measurement of plasma Aβ peptides (and ratios) in FAD. In a study of 66 family members (39 carriers vs 27 non-carriers) we found elevations in plasma Aβ42:40 ratios in carriers compared to non-carriers and differences in Aβ ratios across genotypes: Aβ42:38 ratios were higher in PSEN1 vs. APP, Aβ38:40 ratios were higher in APP vs. PSEN1. Importantly, more aggressive PSEN1 mutations (earlier AAO) had higher Aβ42:40 and Aβ42:38 ratios: in-vivo evidence of pathogenicity of peptide profiles. Plasma Aβ profiles may improve prediction of an FAD individual's likely age at onset and thereby help in trial inclusion and staging.

Hide

PRE-RECORDED: METABOLIC CHANGES IN MICROGLIA AND THEIR EFFECT ON NEUROTOXICITY IN PARKINSON'S DISEASE

Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 113
Lecture Time
04:15 PM - 04:30 PM

Abstract

Abstract Body

Parkinson's disease (PD) , a neurodegenerative disease, is associated with impairment with motor activity and rigidity. The genetic risks of the disease is reported to be between 5 and 10%. It was suggested that activated microglia may play a role in neurotoxicity to dopaminergic neurons (Lazdon et al JNC 2019). We found that reduction in DJ-1 protein ( found in PD patients) in microglia increase both their pro-inflammatory profile and neurotoxicity. Autophagy is an important mechanism for the degradation of intracellular proteins and organelles. We discovered that impaired DJ-1 microglia exhibit an impaired autophagy-dependent degradation of p62 and LC3 proteins, an important protein in the autophagy flux. We discovered that impaired autophagy affects the ability of DJ-1 microglia to uptake αSyn. Further research suggests that αSyn affects microglia metabolism both in vitro and in vivo, leading to their neurotoxic properties. Targeting those metabolic changes in microglia may lead to new therapeutic avenues in the disease.

Hide

PRE-RECORDED: THE PROBABILISTIC AMYLOID CASCADE HYPOTHESIS OF ALZHEIMER’S DISEASE

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 112
Lecture Time
07:00 PM - 07:15 PM

Abstract

Abstract Body

The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, a deterministic chain of events leading from amyloid and then tau deposition, to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the challenges of developing amyloid-targeting drugs, the amyloid hypothesis needs to be reconsidered. We propose a probabilistic model of AD, in which amyloid is still a key player, but the pathogenic weight of amyloid and stochastic factors is inversely proportional to the penetrance of genetic factors. The model identifies three variants of AD: autosomal-dominant AD, APOE ɛ4-related sporadic AD and APOE ɛ4-unrelated sporadic AD. Together, these variants account for a large share of the neuropathological and clinical variability observed in people with AD. The implementation of this model in research might lead to a better understanding of disease pathophysiology, a revision of the current clinical taxonomy , and accelerated development of strategies to prevent and treat this disease.

Hide

PRE-RECORDED: THE HEALTHY BRAIN INITIATIVE: EXAMINATION OF RESILIENCE AND VULNERABILITY FACTORS TO DISTINGUISH HEALTHY BRAIN AGING FROM NEURODEGENERATIVE DISEASE

Session Type
SYMPOSIUM
Date
Sun, 20.03.2022
Session Time
11:35 AM - 01:35 PM
Room
ONSITE: 112
Lecture Time
01:20 PM - 01:35 PM

Abstract

Abstract Body

AIMS: There is increasing interest in primary, secondary, and tertiary prevention approaches to address mild cognitive impairment (MCI) and Alzheimer’s disease and related dementias (ADRD). A significant challenge is measurement of resilience and vulnerability factors that can (a) distinguish between healthy brain aging and MCI/ADRD, and (b) serve as intervention targets. To address this challenge, we created the Resilience Index (RI), a quantifiable measure of brain health, and the Vulnerability Index (VI), a weighted measure of MCI/ADRD risk.

METHODS: We analyzed 241 participants completing a comprehensive clinical-cognitive evaluation. Six lifestyle factors (physical activity, cognitive activity, social engagement, dietary patterns, mindfulness, cognitive reserve) were combined to derive the RI. Twelve easily-obtained sociodemographic, medical, and functional factors were used to develop the VI.

RESULTS: The RI had a 9-fold odds ratio to discriminate individuals with and without cognitive impairment. Individuals with high RI scores (>143) had better cognitive, functional, and behavioral ratings than individuals with low RI scores. The VI had a 17-fold odd ratio to discriminate individuals with and without cognitive impairment. Individuals with high VI scores (≥8) had worse cognitive, functional, and behavioral ratings than those with low VI scores. Combining RI and VI scores differentiated between healthy controls and MCI/ADRD and provided insight into risk of transition/conversion.

CONCLUSIONS: The RI and VI are brief yet powerful indices of brain health and risk of MCI/ADRD. Combining resilience and vulnerability could provide a guide to develop personalized prevention plans to support brain health and identifying asymptomatic individuals for risk of MCI/ADRD.

Hide

ABETA-STRUCTURE PREDICTS CLINICAL ALZHEIMER’S 17 YEARS BEFORE CLINICAL CONVERSION

Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 112
Lecture Time
10:10 AM - 10:25 AM

Abstract

Abstract Body

We verified the performance of Abeta misfolding as a prescreening plasma biomarker for AD as recently shown [1,2,3] with an extended observation period up to 17 years before clinical onset. Additionally, the structure biomarker was compared to the concentration biomarkers GFAP, NFL and ptau181 [4].

Baseline plasma samples of 308 subjects taken between 2000-2002 were analyzed using the infrared-immuno-sensor (iRIS) [3]. The obtained structure biomarker results were compared with GFAP, NFL and ptau181 levels measured with SIMOA.

All biomarkers showed significant alterations in the 17 year old baseline samples of later AD patients compared to the healthy control subjects [4]. However, the structure biomarker showed the best prognostic performance at 17-year follow-up relative to all concentration biomarkers. Additionally, a biomarker panel of the structure biomarker and GFAP levels showed an added value. Interestingly, the prognostic performance of ptau181 was limited to about 8 years before symptom onset. It could not predict AD conversion much more than 8 years in advance.

The structure plasma biomarker identifies individuals with high risk to develop AD up to 17 years before clinical onset [4]. This allows screening by a simple blood test of the aging population for prevention and early intervention in symptom-free stages.

1. Nabers A, et al. EMBO Mol. Med. 2018

2. Stockmann J and Verberk I, et al. Alz Res and Ther. 2020

3. Nabers A, et al. J. Biophotonics. 2016

4 . Léon Beyer and Hannah Stocker, Dan Rujescu, Bernd Holleczek, Julia Stockmann, Andreas Nabers, Hermann Brenner, Klaus Gerwert. submitted


Hide

PRE-RECORDED: CRYO-EM STRUCTURES OF AMYLOID FILAMENTS FROM HUMAN BRAIN

Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:15 PM
Room
ONSITE: 112
Lecture Time
05:30 PM - 05:45 PM

DO VASCULAR RISK SCORES PREDICT CEREBRAL VASCULAR LESIONS?

Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 112
Lecture Time
05:15 PM - 05:30 PM

CARBON MONOXIDE AT LOW DOSES REDUCES DOPAMINE CELL LOSS AND ALPHA-SYNUCLEIN PATHOLOGY IN MODELS OF PARKINSON’S DISEASE

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
05:15 PM - 06:45 PM
Room
ONSITE: 113
Lecture Time
06:15 PM - 06:30 PM

Abstract

Abstract Body

Aims: Exposure to low doses of carbon monoxide (CO) may underlie the reduced risk of Parkinson’s disease (PD) among smokers. Here, we set out to evaluate the neuroprotective potential of low-dose CO treatment in PD models.

Methods: In the AAV-alpha-synuclein (aSyn) model, rats underwent right nigral injection of AAV1/2- asynA53T and left injection of empty AAV, and were treated with oral CO drug product (HBI-002 10ml/kg, daily by gavage) or vehicle. HBI-002 is under development by Hillhurst Pharmaceuticals. In the short-term MPTP model (40mg/kg, i.p.), mice were treated with inhaled CO (iCO) (250ppm) or air. HPLC measurement of striatal dopamine, immunohistochemistry for nigral aSyn and tyrosine hydroxylase, stereological cell counting, and biochemical analyses were conducted blinded to treatment condition.

Results: Each HBI-002 treatment increased carboxy-hemoglobin to 6%. Administration of HBI-002 in the aSyn model reduced ipsilateral loss of both striatal dopamine and TH-positive neurons in the substantia nigra pars compacta compared to rats treated with HBI-002 vehicle. HBI-002 reduced aSyn aggregates and S129 phosphorylation. MPTP-exposed mice treated with low dose iCO had higher dopamine levels and more TH+ neurons than those treated with air. In saline-treated mice, iCO had no effect on striatal dopamine levels or TH+ cell counts. HBI-002 upregulated heme oxygenase-1 and HIF-1α.

Conclusions: These results demonstrating reduced dopamine cell death and aSyn pathology advance low dose CO as a potential neuroprotective strategy for PD.

Hide

PRE-RECORDED: DEMENTIA COMES TO PARKINSON DISEASE: MOLECULAR BASES AND HOW TO DETECT THEM

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE PLENARY: 115-117
Lecture Time
07:00 PM - 07:15 PM

Abstract

Abstract Body

Aims: The goal of this study was to identify the molecular bases of dementia in Lewy body diseases, and highlight ways to detect them in life.

Background: Dementia early in the course of disease is one of the defining features of DLB; cognitive impairment and dementia occur later in the course of idiopathic PD but eventually affect >80% by the time of death. As a prelude to developing neuroprotective treatment, it is necessary to identify the putative causes as early as possible.

Methods & Results: We have performed amyloid PET scans in subjects with PD, PDD and DLB, and conducted autopsies on 20 of these. Amyloid Abeta burden is high in most DLB and in many PDD patients; it is associated with faster cognitive decline. Abeta burden is significantly correlated with the extent of tau positive neurofibrillary tangles and alpha-synuclein positive Lewy bodies measured at autopsy.

Conclusions: We conclude that Abeta is a substantial risk factor for developing dementia in Lewy body diseases, that the combination of Abeta, tau and alpha-synuclein is especially neurotoxic, and speculate that efforts to reduce brain Abeta burden may retard cognitive loss in Lewy body diseases.

Hide

THERAPEUTIC TARGETING OF MICROGLIAL FUNCTIONS

Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:00 PM
Room
ONSITE: 113
Lecture Time
04:15 PM - 04:30 PM

Abstract

Abstract Body

Triggering receptor expressed on myeloid cells 2 (TREM2) is essential for the transition of homeostatic microglia to a disease-associated microglial state. To enhance TREM2 activity, we sought to selectively increase the full-length protein on the cell surface via reducing its proteolytic shedding by A Disintegrin And Metalloproteinase (i.e., a-secretase) 10/17. We screened a panel of monoclonal antibodies against TREM2, with the aim to selectively compete for α-secretase-mediated shedding. Monoclonal antibody 4D9, which has a stalk region epitope close to the cleavage site, demonstrated dual mechanisms of action by stabilizing TREM2 on the cell surface and reducing its shedding, and concomitantly activating phospho-SYK signaling. 4D9 stimulated survival of macrophages and increased microglial uptake of myelin debris and amyloid β-peptide in vitro. In vivo target engagement was demonstrated in cerebrospinal fluid, where nearly all soluble TREM2 was 4D9-bound. Moreover, in a mouse model for Alzheimer’s disease related pathology, 4D9 reduced amyloidogenesis, enhanced microglial TREM2 expression, and reduced a homeostatic marker, suggesting a protective function by driving microglia toward a disease-associated state.

Hide