Tau oligomers trigger inflammation in the eyes of the Alzhiemer’s disease mouse models

Abstract

Purpose: Neurofibrillary tangles (NFT’s) are a pathological hallmark of neurodegenerative tauopathies. Recent findings suggest that tau oligomers, a precursor to NFT’s, are the true neurotoxic tau entities in these diseases. This study is undertaken to determine if the accumulation of tau oligomers initiate inflammatory response in the eyes of Alzheimer’s disease mouse models.

Methods: Eyes from wild type, htau (overexpressing human tau) and P301L (mutant tau) mouse models were dissected and processed for cryosections. Immunohistochemistry was performed using anti-T22 oligomer specific antibody, anti-tau 5 (for total tau) and GFAP (Glial cell) and Iba1 (microglia) antibodies. Images were then captured using a confocal fluorescence microscope. In addition, Western blot of eye homogenates were performed using antibodies for tau oligomers (T22) and tau 5.

Results: Tau oligomers and total tau proteins were detected in the ganglion cells and upto outer nuclear layers of the retina in the AD mouse models and were also confirmed by Western blots. GFAP positive Muller cell processes were seen extending from the ganglion cell layer to the inner nuclear layer. A few of their cell bodies colocalized with the tau oligomers suggesting the engulfment of the oligomers by the Muller cells. Increased number of hyperactivated astrocytes were noted in both the transgenic mouse models mostly at the vicinity of the oligomer deposits in all the cell layers of the retina. In addition, extensive staining of the Iba1 antibody was prominent in the plexiform and nuclear layers of the tau transgenic models indicating microglia activation. Age-matched wild type did not show any signs of inflammation.

Conclusions: Our findings provide evidence of inflammation associated with tau-oligomers in the retina of the tau-transgenic mouse models and that tau oligomers play a vital role in the pathogenesis of Alzheimer’s disease.