International Journal of Molecular Sciences · 6 authors, 5 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
This study demonstrates that acrolein-induced sporadic Alzheimer's disease (sAD) in mice leads to retinal abnormalities, including increased Aβ and p-Tau deposition, reduced retinal nerve fiber layer thickness, decreased electroretinogram b-wave amplitudes, and mild retinal venous beading. These findings suggest that retinal changes in sAD may serve as a valuable model for studying AD-related retinal pathology and potential early diagnostic markers.
**Background:** Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, with sporadic AD (sAD) accounting for approximately 95% of cases. The retina, as an extension of the central nervous system, exhibits pathological changes in AD, including Aβ plaques and p-Tau tangles. Acrolein, an environmental and endogenous toxin, has been implicated in AD pathogenesis. This study investigates retinal abnormalities in a novel sAD mouse model induced by acrolein.
**Methods:** Male C57BL/6 mice (7-8 weeks old) were gavage-fed acrolein (3.0 mg/kg/d) or ultrapure water for 1, 2, or 3 months. Cognitive function was assessed using the Morris water maze test (MWMT) and step-through test (STT). Olfactory function was evaluated with the buried food pellet test (BFPT). Retinal structure was analyzed by optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining. Retinal function was measured via flash electroretinogram (ffERG) under dark-adapted (0.01 and 3.0 cd·s·m⁻²) and light-adapted (3.0 cd·s·m⁻²) conditions. Aβ and p-Tau levels were assessed by Western blot, immunohistochemistry (IHC), and thioflavin T (ThT) staining. Retinal vasculature was examined using color fundus photography and fundus fluorescence angiography (FFA). Intraocular pressure (IOP) was measured with a handheld tonometer.
**Key Results:** Acrolein-treated mice showed significant cognitive impairment in MWMT (reduced platform crossings at 3 months, p<0.01) and STT (increased errors at 1 and 3 months, p<0.05 and p<0.01; decreased latency at 1 and 3 months, p<0.001 and p<0.01). Olfactory dysfunction was observed (increased latency at 1 and 3 months, p<0.001 and p<0.05). Retinal Aβ and p-Tau deposition increased: ThT-positive plaques were significantly elevated at 1 month (p<0.001), 2 months (p<0.01), and 3 months (p<0.001), mainly in the outer nuclear layer (ONL). p-Tau deposition was increased in the retinal nerve fiber layer/ganglion cell layer (RNF/GCL) and inner nuclear layer (INL). Retinal structure: OCT showed significant RNF/GCL thinning at 2 months (p<0.05) and 3 months (p<0.01); H&E confirmed RNFL thinning at 2 months (p<0.05) and 3 months (p<0.001). Total retinal thickness was unchanged. Retinal function: Dark-adapted 0.01 ERG (rod response) showed no significant changes. Dark-adapted 3.0 ERG (rod-cone response) revealed significantly decreased b-wave amplitude at 2 and 3 months (both p<0.05). Light-adapted 3.0 ERG (cone response) showed significantly decreased b-wave amplitude at 2 and 3 months (both p<0.01). IOP was not significantly different between groups. Retinal vasculature: Color fundus photography revealed an aperture with clear boundary in the 3-month acrolein group. FFA showed no leakage but slight retinal venous beading in the 3-month acrolein group.
**Clinical Implications:** This study provides the first evidence that acrolein-induced sAD in mice leads to retinal abnormalities, including Aβ and p-Tau deposition, RNFL thinning, reduced ERG b-wave amplitudes, and mild retinal vascular changes. These findings suggest that retinal changes may serve as a non-invasive biomarker for early detection of sAD. The model mimics clinical sAD pathology and may facilitate research into AD diagnosis and treatment. Further studies are needed to explore the temporal sequence of retinal versus brain changes and to validate these findings in human sAD patients.