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Depressive symptoms and amyloid pathology

Wiels, Wietse A.; Oomens, Julie E.; Engelborghs, Sebastiaan; Baeken, Chris; von Arnim, Christine A.F.; Boada, Mercè; Didic, Mira; Dubois, Bruno

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective: To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education...


Genetic associations between modifiable risk factors and Alzheimer disease

Luo, Jiao; Thomassen, Jesper Qvist; Bellenguez, Céline; Grenier-Boley, Benjamin; de Rojas, Itziar; Castillo, Atahualpa; Parveen, Kayenat

Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire n...


Association of rare APOE missense variants V236E and R251G with risk of Alzheim...

Le Guen, Yann; Belloy, Michael E.; Grenier-Boley, Benjamin; de Rojas, Itziar; Castillo-Morales, Atahualpa; Jansen, Iris; Nicolas, Aude

Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide crit...


Common variants in Alzheimer's disease and risk stratification by polygenic ris...

de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E.; Pedersen, Nancy L.; Stringa, Najada

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Her...


Clinical value of cerebrospinal fluid neurofilament light chain in semantic dem...

Meeter, Lieke H. H.; Steketee, Rebecca M. E.; Salkovic, Dina; Vos, Maartje E.; Grossman, Murray; McMillan, Corey T.; Irwin, David J.; Boxer, Adam L.

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FT...


Prevalence of cerebral amyloid pathology in persons without dementia

Jansen, Willemijn J.; Ossenkoppele, Rik; Knol, Dirk L.; Tijms, Betty M.; Scheltens, Philip; Verhey, Frans R. J.; Visser, Pieter Jelle; Aalten, Pauline

Importance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as meas...


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