Unraveling the mystery of Alzheimer's Disease-related synaptic degeneration

Project objectives

It is widely believed that memory loss, one of the first clinical signs of Alzheimer's disease (1,2), may be caused by changes in synaptic function rather than neuronal loss. In particular, studies of brain imaging functional studies reveal mild functional alterations at the hippocampal level before the clinical diagnosis of AD and in the absence of brain atrophy, suggesting an altered functional connectivity of the hippocampus in the early stages of the disease. Furthermore, there is several evidences that support the thesis according to which dendritic spines are the first synaptic elements to degenerate in the early stages of cognitive decline (3,4).

The aim of this project, which draws on the interdisciplinary expertise of three Units with expertise in the study of brain structures relevant to Alzheimer's disease, is a) to identify molecular characteristics that determine the early degeneration of dendritic spines in biopsy samples from subjects affected by MCI (Mild Cognitive Impairment); b) to study the molecular mechanisms underlying early degeneration of dendritic spines in a mouse model of Alzheimer's disease.

1. D'Amelio and Rossini, Prog Neurobiol. 2012;99,42-60.

2. D'Amelio et al., Trends Neurosci. 2012; 35,700-9.

3. Scheff, S. W. et al. Neurology. 2007; 68,1501-8.

4. D'Amelio et al. Nat Neurosci. 2011;14, 69-76.

Start and end date

2014 - 2017

Project Manager

Prof. Marcello D'Amelio, Coordinator

Coordinating institution of the project

Campus Bio-Medico University of Rome

Other Institutions involved

• IRCCS Santa Lucia Foundation, Rome
• Istituto Superiore di Sanita
• Sapienza University of Rome

Funding source(s).

Ministry of Health