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D. Aggarwal, F. N. Ross-Cisneros, A. A. Sadun; Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimer's Disease Optic Nerve and Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1548.
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© ARVO (1962-2015); The Authors (2016-present)
The receptor for advanced glycation end products (RAGE) and amyloid-beta have both been implicated in the pathogenesis of Alzheimer’s disease (AD) in brain. Previous studies performed in our lab have demonstrated increased expression of RAGE in AD optic nerves, hence suggesting a possible causative role in AD optic neuropathy. This study aimed to characterize the presence of amyloid- beta (a RAGE ligand) and its precursor protein in optic nerves and retinas from patients with AD.
Formalin-fixed, paraffin-embedded 5µm sections of 30 optic nerves and retinas from 15 donors previously diagnosed with AD and 30 age-matched control optic nerves and retinas from 15 individuals with no AD, other neurodegenerative diseases, diabetes mellitus, or sepsis were stained with antibodies reactive against amyloid-beta (AB) and amyloid precursor protein (APP). The tissue sections were counterstained with hematoxylin and observed on a Zeiss Axioskop light microscope. The intensity of immunolabeling for AB and APP was qualitatively graded on a scale of 0 to 3. Grade 0 was defined as no staining, Grade 1 as mild staining, Grade 2 as moderate staining, and Grade 3 as strong staining.
AD optic nerves demonstrated increased immunoreactivity (Grade 3) for AB and APP in a subpopulation of axons and in the cytoplasm of glial cells. Axonal staining was diffuse throughout most of the bundles. Many of these bundles displayed a large "cluster" of axons positively staining for both AB and APP. AD staining in the optic nerve was independent of age. Age-matched control optic nerves also showed staining for AB and APP in a subpopulation of axons and cytoplasm of glial cells, but their staining was less (Grades 1-2) and appeared to increase with age. AD retina showed immunoreactivity for AB and APP primarily in retinal ganglion cells (RGCs) and in the nerve fiber layer (RNFL), displaying Grade 3 staining regardless of age. Age-matched retina demonstrated Grades 1-2 staining AB and APP within these same structures, again increasing with age.
Both amyloid-beta (AB) and amyloid precursor protein (APP) appear to be present in AD and normal optic nerves and retinas. However in Alzheimer's there was a greater accumulation of these proteins suggesting a pathologic role for them in this disease. Eyes continue to be a reliable surrogate for the brain in modeling and demonstrating manifestations of AD.
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