Amyloid-beta and phosphorylated tau in post-mortem Alzheimer’s disease retinas

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.

Progressive chorioretinal involvement in a patient with light-chain (AL) amyloidosis: a case report

“…The same might be true for the choroid. Similarly, amyloid deposits have been found on the retina in diseases such as Alzheimer's disease and cerebral amyloid angiopathy [21,22].…”

Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

“…Given that our group and others have demonstrated the existence of retinal Aβ deposits in AD patients [3,25,46,47,50], our next question was whether vascular PDGFRβ loss is associated with increased vascular Aβ deposition in postmortem retinas from MCI and AD patients. To this end, we studied retinal vascular Aβ 42 pathology in a cohort of age-and sex-matched human eye donors (n = 31, avg.…”

“…Among key findings were severe optic nerve and retinal ganglion cell (RGC) degeneration, thinning of the retinal nerve fiber layer (RNFL), glial stress, altered electroretinography responses, and vascular abnormalities [26,32,37,47,76]. Notably, the pathological hallmarks of AD-Aβ plaques and tauopathy-were further identified in the retina of AD patients, including early-stage cases [25,46,47,50]. Noninvasive high-resolution retinal imaging technologies such as fundus imaging, optical coherence tomography (OCT), as well as recently developed OCT angiography [42,62,72], retinal amyloid imaging [46][47][48], and retinal hyperspectral imaging [35,59] incentivize the use of feasible and inexpensive retinal imaging in the clinical setting to improve AD screening and monitoring.…”

Detection of amyloid-beta and tau in tear fluid of patients with Alzheimer’s disease

“…The most well-known examples of biological differences between AD patients and healthy controls are widespread retinal ganglion cell losses, retinal nerve ber layer (RNFL) thinning and optic nerve degeneration (1)(2)(3)(4). At the biochemical level, amyloid-beta plaques have been observed in postmortem retina samples of AD patients (5), although others have failed to reproduce these results (6). In addition, tau accumulation was identi ed in postmortem retina samples of AD patients (6).…”

“…At the biochemical level, amyloid-beta plaques have been observed in postmortem retina samples of AD patients (5), although others have failed to reproduce these results (6). In addition, tau accumulation was identi ed in postmortem retina samples of AD patients (6). Previous studies also found soluble amyloidbeta in aqueous humor (7) and vitreous body (8) of cognitively healthy persons.…”