Levels of Retinal Amyloid-β Correlate with Levels of Retinal IAPP and Hippocampal Amyloid-β in Neuropathologically Evaluated Individuals

BACKGROUND: Previous studies have used immunohistology to demonstrate Alzheimer’s disease (AD) characteristic accumulation of amyloid-β (Aβ) in the retina of AD patients, a finding indicating retina examination as a potential diagnostic tool for AD pathology. OBJECTIVE: To further explore this idea by investigating whether levels of Aβ(42) and Aβ(40) in retina are associated with corresponding levels in hippocampus, neuropathological assessments, apolipoprotein E (APOE) genotype, and levels of islet amyloid polypeptide (IAPP). METHODS: Levels of high molecular weight (HMW) Aβ(42), Aβ(40), and IAPP in ultra-centrifuged homogenates of retina and hippocampus from patients with AD, multiple sclerosis, AD with Lewy bodies, and non-demented controls were analyzed using Mesoscale Discovery electrochemiluminescence technology employing immunoassay and enzyme-linked immunosorbent assay. RESULTS: Higher levels of retinal and hippocampal Aβ(42-HMW), Aβ(40-HMW), and IAPP(-HMW) were found in individuals with high neuropathological scores of Aβ plaques and in individuals carrying the APOE ɛ4 allele. The retinal levels of Aβ(42-HMW) and Aβ(40-HMW) correlated with corresponding levels in hippocampus as well as with neurofibrillary tangles (NFT) and Aβ scores. Retinal IAPP(-HMW) correlated with retinal levels of Aβ(42-HMW) and with NFT and Aβ scores. CONCLUSION: These results show that different isoforms of Aβ can be detected in the human retina and moreover support the growing number of studies indicating that AD-related pathological changes occurring in the brain could be reflected in the retina.