A5000461472- Alzheimer's disease research and treatments
- Cholesterol and Lipid Metabolism
- Hormonal Regulation and Hypertension
- GDF15 and Related Biomarkers
- Dementia and Cognitive Impairment Research
- Peroxisome Proliferator-Activated Receptors
- Protein Hydrolysis and Bioactive Peptides
- Tryptophan and brain disorders
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
Délégation Paris 5
2015-2016
Université Paris Cité
2015-2016
Université Paris-Sud
2015
Inserm
2011-2015
CEA Paris-Saclay - Etablissement de Fontenay-aux-roses
2014-2015
Université Paris-Saclay
2015
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2015
Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The component altered cholesterol metabolism are closely linked, but the relationship between pathology currently unclear. Brain synthesized in situ cannot cross blood-brain barrier: to be exported from central nervous system into blood circuit, excess must converted 24S-hydroxycholesterol 24-hydroxylase encoded CYP46A1 gene. In AD patients, concentration of plasma cerebrospinal fluid lower than healthy controls....
Alzheimer’s disease (AD) is the most frequent form of dementia in elderly and no effective treatment currently available. The mechanisms triggering AD onset progression are still imperfectly dissected. We aimed at deciphering modifications occurring vivo during very early stages AD, before development amyloid deposits, neurofibrillary tangles, neuronal death inflammation. Most current models based on Amyloid Precursor Protein (APP) overproduction beginning from utero, to rapidly reproduce...
Emerging evidences suggest a link between brain cholesterol homeostasis and Alzheimer disease (AD), particularly in the production of amyloid Aß peptides from protein precursor (APP). However, AD-like Tau pathology has not yet been established. In brain, is synthesized situ but cannot be degraded nor cross blood barrier. The major exportable form 24-hydroxycholesterol (24-OHC) generated by neuronal 24-hydroxylase enzyme (CYP46A1). THY-Tau22 mouse exhibits progressive neuron-specific...
One of the main feature Alzheimer's Disease (AD) is impaired clearance amyloid β peptide (Aβ) from brain, a process facilitated by Apolipoprotein E (ApoE), most influential genetic risk factor for sporadic AD. Among 3 human alleles (ApoE2, ApoE3 and ApoE4), ApoE2 described as reducing probability to develop In order evaluate therapeutic effects overexpression treat AD, we induced production astrocytes (cell type physiologically expressing ApoE) mean GFA2 promoter. We used APP/PS1ΔE9 mouse...
Alzheimer's disease (AD), the most common form of dementia, is characterized by an impaired clearance amyloid β peptide (Aβ) from brain. This process mediated upon its binding with Apolipoprotein E (APOE), influential genetic risk factor for late-onset sporadic AD. Among 3 human APOE alleles (APOE ε2, ε3 and ε4), APOE2 associated a reduced probability to develop disease. In order evaluate therapeutic effects overexpression alleviate AD physiopathological changes, we exogenously expressed in...
Alzheimer's disease (AD) is the most frequent form of dementia and no treatment yet available. We describe here development an alternative AAV-based mouse model with two major objectives. First, to create a relevant closer human physiopathology second, mimic early stages AD. This was obtained by co-injection in hippocampus wild-type mice AAV vectors coding Amyloid Protein Precursor (APPsl) Presinilin 1 (PS1M146L). Our strategy allows stable expression transgenes without significant...
The development of late onset Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition amyloid-ß (Aß) peptides, a hallmark pathology, abnormally retained in AD neurons. In brain, synthesized situ but cannot be degraded nor cross blood-brain-barrier. major exportable form brain 24S-hydroxycholesterol, an oxysterol generated by neuronal 24-hydroxylase encoded CYP46A1 gene. We previously demonstrated that increasing gene...