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Amyloid pathology and vascular disease in focus: exploring interaction in two pathways towards neurodegeneration.

Projectomschrijving

Schade aan bloedvaten in de hersenen en samenklontering van het amyloïd-bèta eiwit zijn de twee belangrijkste ontstaanswijzen van dementie. Deze processen komen onafhankelijk van elkaar voor, maar kunnen elkaar ook beïnvloeden.

Werkwijze

Wat is de invloed van deze wisselwerking? Om hier achter te komen, brengen de onderzoekers de samenklontering van het amyloïd-bèta eiwit in beeld met behulp van een PET-scan bij 700 mensen die meedoen aan de Rotterdam Studie. Dit is een langlopend bevolkingsonderzoek onder meer dan 15.000 mensen van 40 jaar en ouder in de Rotterdamse wijk Ommoord. In deze studie wordt ook vaatschade in de hersenen al 25 jaar nauwkeurig in beeld gebracht. Door de informatie over samenklontering van amyloïd-bèta te combineren met de al aanwezige informatie over vaatschade, kan de rol en de relatie van deze twee processen in het ontstaan van cognitieve problemen tot in detail worden onderzocht.

Producten

Titel: Resistance to developing brain pathology due to vascular risk factors: the role of educational attainment
Magazine: Neurobiology of Aging
Titel: Resistance to developing brain pathology due to vascular risk factors: the role of educational attainment
Auteur: Joyce van Arendonk 1, Pinar Yilmaz 1, Rebecca Steketee 2, Jendé L Zijlmans 3, Sander Lamballais 4, Wiro J Niessen 5, Julia Neitzel 1, M Arfan Ikram 3, Meike W Vernooij 6
Magazine: Neurobiology of Aging
Link: https://pubmed.ncbi.nlm.nih.gov/34298318/
Titel: Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study
Auteur: Joyce van Arendonk 1 2, Julia Neitzel 1 2 3, Rebecca M E Steketee 1, Daniëlle M E van Assema 1 4, Henri A Vrooman 1, Marcel Segbers 1, M Arfan Ikram 2, Meike W Vernooij 1 2
Magazine: Brain
Link: https://pubmed.ncbi.nlm.nih.gov/36374264/
Titel: Predicting amyloid-beta pathology in the general population
Magazine: Alzheimer's & Dementia
Titel: Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study
Magazine: Brain

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Samenvatting van de aanvraag

Central to the quest for the etiology of Alzheimer’s disease is insight into how the two prevailing pathways, amyloid-ß pathology and vascular pathology, influence disease development in its earliest stage. Vascular pathology and amyloid-ß pathology could act as independent processes leading to dementia. Alternatively, both pathways may directly influence each other, interact and cause an accelerated disease process. Evidence from the two pathways influencing each other comes from both experimental studies and patient-based studies. Yet, there is a void of studies that use an integrated approach to study both pathways simultaneously, in particular in a preclinical setting. Technical developments in imaging amyloid-ß deposition non-invasively with use of radioactive PET tracers has greatly advanced the possibility to study amyloid-ß pathology in vivo, directly, in presumed healthy individuals. This proposal will make use of the existing infrastructure within The Rotterdam Study, a large on-going population-based study with extensive multiple time-point data (including brain magnetic resonance imaging), enabling a detailed assessment of vascular pathology. In a sample of 700 subjects from this cohort with varying degrees of vascular pathology, we will acquire brain amyloid PET, and will assess how (progression of) systemic vascular pathology and vascular brain pathology (operationalised as infarcts, white matter lesion burden and microbleeds) relates to amyloid-ß pathology. Furthermore, we will study how amyloid-ß and vascular pathologies interact in their association with cognitive function and cognitive decline over time. This is particularly relevant as vascular factors are potentially modifiable and thus could prove preventive targets for Alzheimer’s disease, especially when shown to modify amyloid-ß pathology.

Onderwerpen

Kenmerken

Projectnummer:
733050817
Looptijd: 100%
Looptijd: 100 %
2018
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Vernooy
Verantwoordelijke organisatie:
Erasmus Medisch Centrum