Abstract
In-vivo labeling of retinal amyloid-beta(Aβ) and tau has potential as non-invasive biomarker for Alzheimer’s disease (AD). However, literature on the presence of Aβ and phosphorylated tau (pTau) in AD retinas is inconclusive. We therefore assessed the presence of Aβ and pTau in post-mortem retinas in 6 AD and 6 control cases who donated brains and eyes to the Netherlands Brain Bank. Neuropathological diagnosis of AD was made according to NIA-AA criteria. Formalin fixed retinas were dissected in quadrants and cross-sections of medial and superior retinas were made. Immuno-histochemical stainings were performed for Aβ, amyloid precursor protein (APP) and pTau. To assess translation to an in-vivo set up using curcumin as labelling fluorophore, co-stainings with curcumin were performed. No typical Aβ-plaques and neurofibrillary tangles, like in the cerebral cortex, were observed in AD retinas. A diffuse immunoreactive signal for pTau was increased in the inner and outer plexiform layers of the retina in AD cases compared to control cases with absence of cerebral amyloid pathology. Immunostaining with anti-Aβ and anti-APP antibodies yielded signal in ganglion cells, amacrine cells, horizontal cells and Müller cells in both control and AD cases. We observed small extracellular deposits positive for anti-Aβ antibodies 12F4 and 6E10 and negative for 4G8 and curcumin. A subset of these deposits could be characterized as corpora amylacea. In conclusion we found that retinal manifestations of AD pathology appear to be different compared to cerebral AD pathology. Using a qualitative cross-sectional approach, we did not find Aβ/APP related differences in the retina between AD and control subjects. In contrast, tau related changes were found to be present in cases with cerebral AD pathology, suggesting retinal tau as a potential biomarker for AD.
Highlights
Alzheimer’s disease (AD) is the leading cause of dementia [1] and its pathology develops 15–20 years before symptom onset [19]
Immunohistochemical detection of amyloid-beta and amyloid precursor protein (APP) in the retina Medial and superior retinal cross-sections were immunostained for Aβ-plaque pathology using anti-Aβ antibodies 6E10 and 12F4
Corpora amylacea are detected in AD and control retina We investigated whether the small 6E10/12F4 positive, 4G8 negative deposits, could be related to corpora amylacea, deposits associated with aging as well as neurodegeneration [29]
Summary
Alzheimer’s disease (AD) is the leading cause of dementia [1] and its pathology develops 15–20 years before symptom onset [19]. Key pathological hallmarks of AD are neuronal loss, extra-cellular accumulation of amyloid-plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing tau [6]. Previous post-mortem studies have investigated the presence of pathological changes in human retinas in AD, the detection of these changes was not consistent across these studies [20]. Neuronal thinning, ganglion cell loss and tau deposition are reported [3, 30]. Aβ deposition was found in whole mounted retinas and cross-sections by three studies from one lab, preferentially affecting the
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