Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer's disease

Abstract

Murine transgenic models of Alzheimer's disease (Tg-AD) have been useful to analyze the contribution of β-amyloid precursor protein (βAPP), Aβ42 peptide deposition, and the proinflammatory mechanisms that characterize Alzheimer-type neuropathology. In this report, we have studied the levels of βAPP, Aβ40 and Aβ42 peptide, as well as the innate immune and inflammatory response-regulator complement factor H in the brain and retina in four different Tg-AD models including Tg2576, PSAPP, 3xTg-AD, and 5xFAD. Aged, symptomatic 5xFAD mice showed the highest retinal abundance of Aβ42 peptides and the highest deficits in complement factor H. This may be a useful model to study the mechanisms of amyloid-mediated inflammatory degeneration. The superior colliculus and retina obtained from late-stage Alzheimer's disease revealed upregulated amyloidogenic and inflammatory signaling along the anteroposterior axis of the retinal-primary visual cortex pathway.

Fig. 1

βAPP, Aβ42, and complement factor H (CFH) levels in transgenic murine models of Alzheimer’s disease (Tg-AD) mouse retina compared with the age-matched controls. The presence of βAPP and Aβ42 peptides suggests a common and functional secretase-mediated processing of βAPP in the Tg-AD retina [8,12,13]; other βAPP-derived peptide fragments in Tg-AD retina have been described [13]. As further discussed in the text, highest relative βAPP, Aβ42, and the lowest relative CFH levels were found in 5xFAD retina. A dashed horizontal line at 5.0 indicates relative CFH levels in PSAPP mice for ease of comparison; N=5; *P<0.05; **P<0.01 (analysis of variance).

Fig. 2

βAPP, Aβ42, and complement factor H (CFH) levels in the Alzheimer visual pathway. Data are shown for control, Alzheimer’s disease retina (AD retina), Alzheimer’s disease superior colliculus (AD-SC), and Alzheimer’s disease primary visual cortex (AD-PVC; Brodmann area A17). The highest βAPP and Aβ42 peptide levels, averaging 19.1-fold to 15.5-fold over age-matched controls respectively, were found in the AD-PVC. A dashed horizontal line at 1.0 indicates relative βAPP, Aβ42 peptides, and CFH levels in age-matched control retina for ease of comparison; N=5; *P<0.05; **P<0.01 (analysis of variance).