Early-Occurring Dendritic Spines Alterations in Mouse Models of Alzheimer’s Disease Inform on Primary Causes of Neurodegeneration

The consensus that synaptic failure is the earliest cause of cognitive deterioration in Alzheimer’s disease (AD) has initially led to investigate structural (dendritic spines) and physiological (LTP) synaptic dysfunctions in mouse models of AD with established cognitive alterations. The challenge is now to track down ultra-early alterations in spines to uncover causes rather than disease’s symptoms. This review article pinpoints dysregulations of the postsynaptic density (PSD) protein network which alter the morphology and function of spines in pre- and early- symptomatic hAPP mouse models of AD, and, hence, inform on primary causes of neurodegeneration.