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BioMed Research International
Volume 2015 (2015), Article ID 291658, 11 pages
Review Article

Integrating Retrogenesis Theory to Alzheimer’s Disease Pathology: Insight from DTI-TBSS Investigation of the White Matter Microstructural Integrity

1Translational Psychiatry Research Group, Department of Clinical Medicine, Federal University of Ceara, Rua Professor Costa Mendes 1608, 4° Andar, Rodolfo Teófilo, 60430140 Fortaleza, CE, Brazil
2Institute for General Medicine, Goethe University, 60590 Frankfurt am Main, Germany
3Department of Psychiatry, Psychotherapy and Psychosomatics, Goethe University, 60528 Frankfurt am Main, Germany
4Alzheimer’s Disease Center, Federal University of Rio de Janeiro (UFRJ), 22290140 Rio de Janeiro, RJ, Brazil
5Department of Cognitive and Behavior Neurology, Federal University of Rio de Janeiro (UFRJ), 22290140 Rio de Janeiro, RJ, Brazil
6Centre for Study and Research on Aging, Instituto Vital Brazil, 22451000 Rio de Janeiro, RJ, Brazil

Received 9 May 2014; Revised 14 October 2014; Accepted 1 November 2014

Academic Editor: W. David Arnold

Copyright © 2015 Gilberto Sousa Alves et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Microstructural abnormalities in white matter (WM) are often reported in Alzheimer’s disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.