Affiliations: [a] Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada, H3G 1Y6 | [b] Department of Anatomy & Cell Biology, McGill University, Montreal, Quebec, Canada, H3G 1Y6 | [c] Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada, H3G 1Y6
Correspondence:
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Corresponding author: Dr. A.C. Cuello, Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1325, Montreal, Quebec, Canada, H3G 1Y6. Tel.: +1 514 398 3617; Fax: +1 514 398 8317; E-mail: [email protected].
Note: [**] Both authors contributed equally to the production of this paper
Abstract: Alzheimer's disease (AD) studies typically focus on the extracellular impact of the amyloid-beta (Aβ) protein, however recent findings also implicate intracellular Aβ (iAβ) accumulation in the disease's molecular neuropathology. In a double mutant transgenic rat model (AβPP and PS1 mutations, UKUR25), stably expressing intracellular human Aβ fragments in an environment devoid of both amyloid plaques and neurofibrillary tangles, we investigated the impact of iAβ burden on both the incidence and relative cross sectional areas of the Golgi apparatus, lysosomes and lipofuscin bodies. Pyramidal cells within the hippocampus and neocortex of both transgenic and non-transgenic age matched controls were compared. This comparison revealed a significant increase in both the proportional area occupied by Golgi apparatus elements as well as in the mean individual cross sectional area of Golgi compartments in the hippocampus of transgenic rats as compared to controls. Elevated lysosome and lipofuscin elements in the hippocampi of transgenic rats were observed, as was an increase in the mean individual, cross sectional area of lipofuscin bodies in the cortex of transgenic rats as compared to controls. These findings support the hypothesis that intracellular Aβ accumulation not only has an impact on subcellular compartments but also potentially contributes to the neuronal cell pathology observed in AD.
