Neuroscience Letters 469 (2010) 214–218 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet A multimodal MRI investigation of the subventricular zone in mild cognitive impairment and Alzheimer’s disease patients Andrea Cherubini a , Ilaria Spoletini a , Patrice Péran b , Giacomo Luccichenti b , Margherita Di Paola a , Giuseppe Sancesario c , Walter Gianni d , Franco Giubilei e , Paola Bossù a , Umberto Sabatini b , Carlo Caltagirone a,c , Gianfranco Spalletta a,∗ a Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy b Department of Radiology, Santa Lucia Foundation, Rome, Italy c Department of Neuroscience, University of Tor Vergata, Rome, Italy d Geriatric Unit, INRCA, Rome, Italy e Department of Neurology, Ospedale Sant’Andrea, Rome, Italy article info Article history: Received 28 October 2009 Received in revised form 21 November 2009 Accepted 30 November 2009 Keywords: Subventricular zone Mild cognitive impairment Alzheimer’s disease DTI abstract The subventricular zone (SVZ) is a region that lies immediately beneath the ependymal layer on the lateral wall of the lateral ventricles, and is separated from the caudate nucleus by a layer of myelin. It contains multipotent neural stem cells. The aim of this study was to investigate the tissue around the SVZ, with the hypothesis that multimodal MRI is able to highlight the progressive disruption of tissue caused by the neurodegenerative disease in this area. We combined volumetric and diffusion tensor (DTI) imaging using a 3 T imager in a cross-sectional study including 30 patients with amnestic-mild cognitive impairment (a-MCI), 30 patients with Alzheimer’s disease (AD) and 30 age- and gender-matched healthy controls (HC). Our data indicate that mean diffusivity (MD) values increase continuously from HC through a-MCI to AD in the bilateral SVZ, where most of the proliferating stem cells in the adult brain are located. This result was specific for the SVZ and could not be observed in other periventricular areas. Multimodal MRI, being able to highlight structural changes of microscopic tissue in humans in vivo, could represent a precious tool to complement histological studies of neurogenesis. © 2009 Elsevier Ireland Ltd. All rights reserved. During the last decade of the 20th century, following the excit- ing discovery of neurogenesis in the adult human brain [10], the possibility has been raised that endogenous progenitor cells, the precursors of new neurons in the adult brain, might be harnessed and manipulated to provide neuronal replacement therapy. These groundbreaking studies highlight further therapeutic opportuni- ties by unrevealing a mechanism of triggering endogenous stem cell activity. In the human adult brain there are two main neurogenic regions that contain multipotent neural stem cells: the subgranular zone of the dentate gyrus in the hippocampus, and the subventricu- lar zone (SVZ). The SVZ is a region that lies immediately beneath the ependymal layer on the lateral wall of the lateral ventricles, and is separated from the caudate nucleus by a layer of myelin [7,10,16]. In the subgranular zone, hippocampal neural stem cells proliferate and migrate into the dentate granule cell layer where ∗ Corresponding author at: Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina, 306, 00179, Rome, Italy. Tel.: +39 0651501575; fax: +39 0651501575. E-mail address: g.spalletta@hsantalucia.it (G. Spalletta). they differentiate into granule cells. Similarly, in the SVZ there is a continuous generation of migrating neuroblasts that are des- tined for the olfactory bulb or for other areas of cell death in the brain. Although classical pathological hallmarks of Alzheimer’s disease (AD) are deposition of senile plaques, accumulation of intracellular neurofibrillary tangles, synapse loss and neuronal damage, prelim- inary work has demonstrated that alteration of other mechanisms, such as neurogenesis, may play an important role in mediating some aspects of neurodegeneration that occur in AD patients [2], possibly in the earlier stages of the disease. In particular, a num- ber of studies have shown impaired neurogenesis, while others demonstrated an increase in neurogenesis, in the hippocampus and other anatomical regions in both transgenic models of AD and in post-mortem tissues of AD patients [1,11,13–15,18]. These results are controversial and the role of altered neurogenic processes and their underlying cellular mechanisms in AD still need to be clarified. However, since direct analysis of in vivo neurogenesis in humans is, for obvious reasons, difficult to obtain, the study of changes in neurogenic areas in living patients during the earlier stages of the disease represents the most promising approach. In fact, it is pos- sible that microarchitecture alterations in neurogenic areas could 0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2009.11.077