Discover the latest publications from the ADAPTED Project.
Generation of a set of isogenic iPSC lines carrying all APOE genetic variants (Ɛ2/Ɛ3/Ɛ4) and knock-out for the study of APOE biology in health and disease
We describe a new set of induced pluripotent stem cells (iPSC) lines carrying common APOE variants (Ɛ2, Ɛ3, and Ɛ3/Ɛ4) and a knock-out isogenic to the parental APOE Ɛ4/Ɛ4 line (UKBi011-A).
Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer’s disease
Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer’s disease (AD). We show that LPAs may contribute to early AD pathogenesis, and that APOE may influence the association between LPAs and Aβ-42.
Alzheimer's Research & Therapy volume 12, Article number: 124 (2020)
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.
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.
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.
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.
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.
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