Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer’s and Parkinson's disease patients: Possible biomarkers for early diagnosis

Abstract

AbstractBackgroundAlzheimer’s disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid‐beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure therefore, the actual challenge is to define new biomarkers and non‐invasive technologies to measure neuropathological changes in vivo at pre‐symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non‐invasive rapid detection of AD biomarkers.MethodHuman retinal slices from AD (n=20) and PD (n = 10) patients and age matched controls (n=20/10) were purchased from Human Eye Biobank for Research, St Michael Hospital, Toronto, Canada. Immunofluorescence analysis was perfomed using primary antibodies to detect protein aggregates, neurodegeneration and glial activation: anti‐βAmyloid; anti‐Cleaved‐Casapase3; anti‐PhosphoTau; anti‐Iba1; anti‐GFAP; anti‐C3d; anti‐IL‐1β; anti‐αsynuclein; anti‐TH, anti‐TuJ1.ResultIn all AD patients we detected retinal Aβ and pTau immunoreactivity and both in the inner and outer layers; Aβ plaques number, in a region of 400 mm2, was significantly higher in AD patients compared to controls (p<0.01). pTau immunoreactivity (AT100 clone) was significantly higher in the AD retina compared to age matched controls as quantified by fluorescence intensity in each field of view (p<0.005). Analysis GFAP staining showed a marked astrogliosis localized at the level of the ganglion cell layer both in AD and PD retinas. Astrogliosis may arise also as a consequence of aging however, the amount of astrocyte activation was more pronounced in the AD and PD retina compared to controls, as quantified by fluorescence intensity in each field of view. Similarly microglia cell density was increased in AD and PD patients retina compared to age matched controls. C3 and Il1β were enhanced in bot AD and PD retina, suggesting a detrimental glial activation.ConclusionThese observations further support the possibility that ocular biomarkers could be used for early detection of AD associated neurodegeneration.