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

• Published in: Journal of Alzheimer's disease Vol. 73; no. 3; pp. 1201 - 1209
• Main Authors: Schultz, Nina, Byman, Elin, Wennström, Malin
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2020
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Apolipoproteins E - genetics; Female; Hippocampus - metabolism; Hippocampus - pathology; Humans; Islet Amyloid Polypeptide - metabolism; Male; Middle Aged; Neurofibrillary Tangles - genetics; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Retina - metabolism; Retina - pathology; amyloid-β; IAPP; Alzheimer’s disease; hippocampus; retina
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-190868

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 Aβ42 and Aβ40 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) Aβ42, Aβ40, 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 Aβ42-HMW, Aβ40-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 Aβ42-HMW and Aβ40-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 Aβ42-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.