ALZHEIMER

Primary cell cultures of neurons with / without astrocytes infected with AAV or LV vectors coding mutated proteins implicated in the pathology
Cortical neurons treated with PDC (glutamate transport inhibitor): chronic excitotoxicity model - Follow up of compounds modulating NMDA receptors
NGF deprived septal cholinergic neurons: model for neurotrophic compounds
Microfluidic compartmentalized neuron cultures: soma is in one compartment and axon in the another one, both compartments being connected to enable amyloid peptide treatment in each compartment

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Aggregation, propagation in each compartment, cell survival

Cell survival, morphological changes, protein measurement, etc.

Transgenic mouse models to study factors/drugs targeting amyloidosis (APP/PS1?E9, 3xTg, huAPP)
Tauopathies (Rat): lentiviral / AAV – Tau or P301L or Tau fused to a pro-aggregating peptide
AAV- hAPP + AAV-hPS1 (mouse and rat)

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Neuropathological evaluation; 3D histology to evaluate local changes statistically; Local glucose consumption; Brain morphometry using high resolution MRI; Amyloid Plaques by Gadolinium-Stained MRI; Perfusion measurement by MRI and resting state fMRI measures; Behavioral changes; etc.

Aß40, Aß42 and Tau quantification, cognitive function (open field, Morris water maze), LTP, etc.

	Parenchymal inoculation of Alzheimer human brain in Microcebus murinus Tauopathies (Macaques): lentiviral or AAV vectors over-expressing different species of tau proteins (WT, P301L, wild-fused to a pro-aggregating peptide)
READ-OUT	Tau, Amyloid, Neuroinflammation and glucose metabolism, PET imaging, MRI, MR spectroscopy, histology, motor and cognitive behavior, etc.

	Clinical investigation Center (Phase I and II), Biological resource center, stratified cohorts of patients
READ-OUT	PET, SPECT, MRI imaging, Markers of amyloid, Tau, neuroinflammation and neuron loss,