Dendritic spines are lost in clusters in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.
This work was supported by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (Grant IJCI-2016-27658 to PMS, Grant PGC2018-094307-B-I00), the Cajal Blue Brain Project (the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland) and the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain). JBP is currently supported by Grants from the Swedish Research Council (#2018-02201), Hjärnfonden (#FO2019-0289), Alzheimerfonden (#AF-930827) and the Strategic Research Programme in Neuroscience at Karolinska Institutet (Stratneuro Startup Grant).