RETINAL PATHOLOGY IN ALZHEIMERS-DISEASE .2. REGIONAL NEURON LOSS AND GLIAL CHANGES IN GCL

Detailed analyses of neuronal and astrocyte cell numbers in the gangli on cell layer (GCL) of whole-mounted peripheral retinas from 16 Alzhei mer's disease (AD) and 11 control eyes (11 and 9 cases, respectively) demonstrate extensive neuronal loss throughout the entire retina in AD as compared to control eyes. The observed neuronal loss is most prono unced in the superior and inferior quadrants, ranging between 40 and 4 9% throughout the midperipheral regions, and reaching 50-59% in the fa r peripheral inferior retina, while the overall neuronal loss througho ut the entire retina amounts to 36.4% (p < 0.004). Although the 16% in crease in astrocyte numbers is not significant, the ratio of astrocyte s to neurons is significantly higher (82%; p < 0.0008) in AD as compar ed to normal retina (0.238 +/- 0.070 vs. 0.131 +/- 0.042). These resul ts are strengthened by the close agreement (within +/- 15% of respecti ve means) found between fellow eyes. Analysis of glial fibrillary acid ic protein immunoreactivity (GFAP-ir) in sections of retinas from an a dditional 12 AD and 19 control cases show increased GFAP-ir with more extensive labeling of astrocytes in the GCL as well as increased label ing of Muller cell end-feet and radial processes in AD as compared to control retinas. The extensive loss of neurons documented in these ret inas, accompanied by an increased astrocyte/neuron ratio, provides fur ther support for the substantial involvement of the retina in AD.