Affiliations: School of Medicine (CVP, MJR), Department of Neurology, University Hospital of Antioquia, Medellin, Colombia
Correspondence:
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Corresponding author: C. Velez-Pardo, School of Medicine, University of Antioquia (UdeA), Cra. 51D no. 62-29, P.O. Box 1226, Medellin, Colombia
Note: [*] This work was financially supported by “Comite para el Desarrollo de la Investigation-CODI-UdeA (grant to CVP)”.
Abstract: Recent studies have shown that the missense mutation in presenilin-1 [E280A] increases deposition of amyloid-ß (Aß[1-42/43]) producing severe cerebellar pathology. Although Aß has been involved as a neurotoxic peptide, its role in neuronal loss in PS-1 [E280A] patients has not yet been established. This study investigated terminal fluorescein 12-dUTP nick-end labeling (TUNEL)-positive cells (neuron, glia and microglial cells) and thioflavine S-stained Aß-plaques and neurofibrillary tangles in the frontal, parietal, temporal, occipital, hippocampus and cerebellum cortices of 3 normal aging and 8 familial Alzheimer's disease patients with the presenilin-1 [E280A] mutation. Using these approaches, we found no obvious correlation between DNA fragmentation and the severity of amyloid-ß deposition (Aß) and neurofibrillary tangle (NFT) formation. Indeed, we only observed 10 out of 48 FAD brain sections displaying TUNEL (+) labeling, and none with the classical apoptotic morphology. These results may indicate that DNA fragmentation is not a generalized phenomenon in early-onset FAD PS1 [E280A] patients or that neuronal cells are dying by a different mechanism of cell death. Taking together these findings suggest that Aß and NFTs are not per se a causative factor to damage neuronal cells but their damage could be more related with individual neuronal vulnerability and brain aging
