Dervis Salih

Abstract Much research into the aetiology of Alzheimer’s disease (AD) has focused on neuronal cell types, while studies on the contribution of glial cells, particularly oligodendrocytes (OLGs), are only starting to emerge. Altered brain DNA methylation, an epigenetic modification that provides the interplay between genetics and environmental cues to tightly regulate gene expression, is well documented in AD. Yet, cell-type-specific investigations remain limited.

Keywords Alzheimer’s disease neurodegeneration cortico-hippocampal circuits cortical layers NMDARs β-amyloid tau synaptic dysfunction memory impairment two-photon calcium imaging Neuropixels Introduction Structured spontaneous activity is a hallmark of the cortico-hippocampal circuits supporting memory-guided cognition.1,2 It arises from recurrent synaptic excitation and balanced inhibition3 and is modulated by synaptic N-methyl-D-aspartate receptors (NMDARs).4,5 In Alzheimer’s disease (AD),...

The amyloid hypothesis of Alzheimer's disease is predicated on data showing that mutations in APP (the gene that encodes for the amyloid precursor protein) and, by implication, amyloid β deposition, drive the formation of tau tangles in the brain of people with Alzheimer's disease, and also in doubly transgenic APP and MAPT mutant mice.This hypothesis is usually drawn as a cell-autonomous process, with amyloid β released outside a neuron, but inducing tangle formation within the same neuron.