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International Journal of Alzheimer’s Disease
Volume 2012, Article ID 752894, 10 pages
Review Article

Lysosomal Fusion Dysfunction as a Unifying Hypothesis for Alzheimer's Disease Pathology

Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, OH 43210, USA

Received 2 June 2012; Revised 1 August 2012; Accepted 2 August 2012

Academic Editor: Wiep Scheper

Copyright © 2012 Kristen E. Funk and Jeff Kuret. 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.


Alzheimer's disease is characterized pathologically by extracellular senile plaques, intracellular neurofibrillary tangles, and granulovacuolar degeneration. It has been debated whether these hallmark lesions are markers or mediators of disease progression, and numerous paradigms have been proposed to explain the appearance of each lesion individually. However, the unfaltering predictability of these lesions suggests a single pathological nidus central to disease onset and progression. One of the earliest pathologies observed in Alzheimer's disease is endocytic dysfunction. Here we review the recent literature of endocytic dysfunction with particular focus on disrupted lysosomal fusion and propose it as a unifying hypothesis for the three most-studied lesions of Alzheimer's disease.