Topic: early onset Alzheimer’s disease

Presenilin1 (PSEN1) E280A mutation causes early onset Alzheimer’s disease (AD) in the world’s largest familial AD kindred. We previously published a case report of a carrier from this kindred who was remarkably protected from cognitive decline for thirty years. Positron emission tomography (PET) brain analysis showed lower levels of Tau pathology relative to typical PSEN1 E280A carriers. Whole-genome sequencing revealed homozygosity for an Apolipoprotein E mutation (Christchurch, APOECh). As the ApoECh mutation is found within the heparan sulfate proteoglycan (HSPG) binding domain, we hypothes

Down syndrome (Trisomy 21, Ts21) is the most common cause of early onset Alzheimer’s disease. We previously reported that secretomes of induced pluripotent stem cell (iPSC)-derived human Ts21 cortical neurons inhibited hippocampal long-term potentiation (LTP) in a tau-dependent manner (Hu et al., Cell Reports, 2018). Here, we employed electrophysiological recording from the CA1 area of the hippocampus of live rats under urethane anaesthesia to assess the ability of anti-tau antibodies to immunodeplete Ts21 iPSC-derived neuron synaptotoxic tau. We found that the mid-region (amino acids 210-241)