No Expression of Proteins Associated with Alzheimer's Disease and Parkinson's Disease in Retina and Lens
Cheng-Ying Ho, Juan Troncoso, Charles Eberhart. The Johns Hopkins Hospital, Baltimore, MD
Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders and together affect more than 30 million people worldwide. Definite diagnosis of AD and PD still relies on postmortem examination of the brain, but the possibility of earlier pathological diagnosis in living patients using abnormal proteins associated with these diseases is increasingly being explored. It has been previously reported that amyloid plaques were detectable non-invasively in the retina and lenses of a very small group of AD patients, but correlations with cortical pathology were limited. We therefor evaluated expression of proteins associated with AD and PD pathology in postmortem eyes in a larger case-control study.
Design: Eyes enucleated at autopsy from 7 cases of AD, 6 cases of PD or PD with dementia, and 6 age-matched controls were retrieved from the brain resource center and autopsy archives of our hospital. The AD cases included 6 cases of definite AD with a CERAD plaque score C and Braak score V-VI/VI, and one case of probable AD with a CERAD score B and Braak score II/VI. The PD cases included 2 cases of Lewy body disease in a brainstem pattern, 3 cases in a limbic pattern and one case in a neocortical pattern. Immunostains for beta-amyloid and phospho-tau and Congo red stains were performed on the AD and control cases. Immunostains for alpha-synuclein were performed on all cases.
Results: Contrary to previously published results, no amyloid deposits were detected in the retinas or lenses by beta-amyloid immunostains or Congo red stains in AD cases. The phospho-tau immunostains also did not reveal any abnormal tau accumulation in AD eyes. Scattered-to-frequent cells in the ganglion cell layer and inner nuclear layer of retina demonstrated diffuse cytoplasmic alpha-synuclein immunoreactivity in 5 of 7 (71%) AD cases, 4 of 6 (67%) PD cases, and 3 of 6 (50%) control cases. However, no definite Lewy bodies or Lewy neurites were identified. The retinal alpha-synuclein positivity and the frequency of the positive cells did not correlate with the presence or extent of the Lewy body pathology in the brain.
Conclusions: Abnormal protein aggregation characteristic of AD and PD is not present in the retinas or lenses of affected patients. Our data call into question the use of tracing dye or other methods to detect AD or PD pathology in the eyes of presymptomatic patients.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 311, Wednesday Afternoon