ADAPTED PUBLICATIONS

Discover the latest publications from the ADAPTED Project. 

CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers

We show that levels of proteins CDH6 and HAGH are significantly higher in AD patients who also carry the APOE ε4 gene,  compared to healthy controls. Our findings suggest that CDH6 and HAGH could be used as new blood-based biomarkers for the detection of presymptomtic AD. 

Scientific Reports volume 10, Article number: 8233 (2020)

PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment

We show a rare coding variant in the PLCG2 gene slows AD disease progression and maintains cognitive function. We observe that this protective effect can apparently counteract the deleterious effect of the APOE ε4 allele.  This highlights the PLCG2 enzyme as a potential target for therapeutic intervention in AD.

Acta  Neuropathologica (2020)

Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s disease

We show an unexpected potential genetic link between echocardiographic measures in healthy populations and cognitive decline in later life. These findings may be important in designing preventative strategies to combat Alzheimer's disease.

Scientific Reports volume 9, Article number: 16665 (2019)

A perfused human blood–brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport

Receptor-mediated transcytosis is one of the major routes for drug delivery of large molecules into the brain. The aim of this study was to develop a novel model of the human blood–brain barrier (BBB) in a high-through-put microfluidic device. This model can be used to assess passage of large biopharmaceuticals, such as therapeutic antibodies, across the BBB.

Fluids Barriers CNS (2018) 15:23

Blood-derived integration-free iPS cell line UKBi011-A from a diagnosed male Alzheimer's disease patient with APOE ɛ4/ɛ4 genotype

Alzheimer's disease (AD) is most the frequent neurodegenerative disease, and the APOE ε4 allele is the most prominent risk factor for late-onset AD. Here, we present an iPSC line generated from peripheral blood cells of a male AD patient employing Sendai virus vectors encoding the transcription factors OCT4, SOX2, KLF4 and c-MYC. The characterized iPSC line expresses typical human pluripotency markers and shows differentiation into all three germ layers, complete reprogramming vector clearance, a normal SNP genotype and maintenance of the APOE ε4/ε4 allele.

 

Stem Cell Research Volume 29, May 2018, Pages 250-253  

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies

Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions.

Alzheimer's & Dementia, 6th January 2018, Pages 707-722

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects.

Nature Genetics volume 49, pages 1373-1384 (2017)

ADAPTED 1st Press Release

To boost the development of new medicines for Alzheimer's disease (AD), a major new European-wide project has now been launched to investigate an area of AD research which has previously received little attention. The ADAPTED (Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development) project focusses on the APOE gene which is well known as a risk factor for developing the disease, but precisely how this gene contributes to the risk of developing AD is not known.

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©2018 ADAPTED

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No 115975. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations