Retinal and Optic Nerve Lesions Correspond to Amyloid in Autosomal Dominant Alzheimer's Disease.

Autosomal dominant Alzheimer's disease (ADAD) is a rare form of Alzheimer's disease (AD) in which the biology of the disease can be explored during the presymptomatic phase of the illness. The retina is an outgrowth of the central nervous system and therefore provides the opportunity for direct observation of neural tissue and its vasculature during life. Retinal thinning measured in vivo has been previously described in persons carrying ADAD mutations through fundoscopy but its pathologic correlates have not been reported. We describe retinal lesions detected using fundoscopy in vivo in a patient homozygous for the A431E mutation in PSEN1 and its pathological correlates. Retinal lesions seen with fundoscopy during life corresponded to intraretinal and prelaminar optic nerve head amyloid β ₄₂ -protein that were surrounded by perivascular anti-11A50-B10-Aβ ₄₀ and gliosis. We then performed a cross-sectional, observational study of forty-one Latinos in three cohorts consisting of (1) persons with ADAD causing mutations, (2) at 50% risk for, but testing negative for ADAD mutations, and (3) elderly subjects not at-risk for ADAD. Clinical exam demonstrated novel, yellow, intraretinal lesions in Cohort 1 in absence of drusen. Fifty-six percent of Cohort 1 subjects had >10 retinal lesions compared to 0% and 25% for Cohorts 2 and 3, respectively ( P < 0.04). There has been some controversy as to the detectability of Aβ in the retina of persons with AD during life and our findings verify the presence of intraretinal, prelaminar, and perivascular amyloidosis detectable during life in a subset of AD patients.