Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects With Alzheimer Disease

Abstract

Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features. We examined one or both eyes from 19 autopsy cases, 17 of which had varying degrees of AD-related changes, and 2 of which were age-matched controls. Three cases had glaucoma and 4 had macular degeneration. Immunohistochemistry for tau, β-amyloid, TDP-43, ubiquitin, and α-synuclein showed no evidence of inclusions, deposits or other protein accumulation in any case, in any part of the globe. This finding suggests that regardless of the severity of changes seen in the brain in AD, there are no similar changes in the globe.

Phosphorylated α‐synuclein in the retina is a biomarker of Parkinson's disease pathology severity

“…This study is the first to demonstrate p‐syn immunoreactive retinal structures similar to brain Lewy bodies and neurites. Previous research using antibodies against α‐syn in thin paraffin sections stated that no pathological α‐syn immunoreactivity could be found in the retina and lens of PD patients or in any part of the ocular globe in AD . Differences with our study may be attributed to our use of antibodies against p‐syn rather than unmodified α‐syn, and our use of retinal whole mounts rather than thin paraffin sections.…”

“…Previous research using antibodies against a-syn in thin paraffin sections stated that no pathological a-syn immunoreactivity could be found in the retina and lens of PD patients 45 or in any part of the ocular globe in AD. 46 Differences with our study may be attributed to our use of antibodies against p-syn rather than unmodified a-syn, and our use of retinal whole mounts rather than thin paraffin sections. The relatively small number of p-syn-positive structures may be difficult to detect in the small tissue volumes available in paraffin sections.…”

Ocular Biomarkers of Alzheimer's Disease: The Role of Anterior Eye and Potential Future Directions

“…[43][44][45][46] In their first study, Michael et al 43 examined 54 lenses (n ¼ 39, from 21 postmortem donors with AD and n ¼ 15, from age-matched controls) using Congo red, thioflavin, and Ab immunohistochemical (monoclonal Ab antibody, clone 6F/3D) staining. They found negative staining in all AD and control lenses.…”

“…They concluded that AD-related aggregates do not deposit in the eye similar to brain deposits, or are present at lower levels or in different forms. In a very recent examination of the eyes of 19 human postmortem cases (17 with AD and two age-matched controls), Williams et al 46 performed hematoxylin and eosin staining as well as Ab immunohistochemistry (clone 6F/3D) and found no evidence of Ab deposits or accumulation in any part of the eye including the lens, concluding that that there may be no concurrent or similar AD alterations in the brain and lens. The different methodologic approaches used in these studies including AD diagnostic criteria, using cross-sections rather than the whole mount tissue and the applied staining protocols, make comparison of outcomes of these studies difficult, but they may account, at least in part, for the reported discrepancies.…”

“…Despite these conflicting reports [43][44][45][46] that questioned the advocated notion of the crystalline lens to serve as an indicator or predictor of AD pathologic changes, the positive and promising outcomes of other studies encouraged investigators to develop noninvasive methods to explore in vivo AD signatures in the human crystalline lens. Kerbage et al 47 first used an in vivo technique of laser scanning along with a fluorescent ligand to examine the presence of AD signatures in the human lens.…”