SignificanceRecessive Stargardt macular degeneration (STGD1) and a subset of cone–rod dystrophies are caused by mutations in the Abca4 gene. The ABCA4 protein is a flippase in photoreceptor cells that helps eliminate retinaldehyde, a toxic photoproduct of vision. Here we found that ABCA4 is additionally present in the retinal pigment epithelium (RPE) of mice at approximately 1% of its abundance in the neural retina. Genetically modified mice that express ABCA4 in RPE but not in photoreceptor cells showed partial rescue of both the lipofuscin accumulation and photoreceptor degeneration observed in Abca4−/− mice and in STGD1 patients. These observations suggest that ABCA4 in the RPE prevents photoreceptor degeneration in Abca4−/− mice and possibly in STGD1 patients.

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Dementia with brainstem and neocortical Lewy bodies (LB) is a source of ongoing nosologic controversy and confusion. Differing opinions about concomitant Alzheimer's disease (AD) have produced competing nomenclatures. We applied neocortical plaque-based criteria for the diagnosis of AD from the National Institute on Aging and from the Consortium to Establish a Registry for AD for definite, probable, and possible AD to 58 dementia brains with LB, 10 elderly nondemented controls, and 58 brains with neuropathologically pure AD. We also employed diagnostic criteria requiring both neocortical plaques and tangles, and assessed the extent of neurofibrillary pathology in all 126 specimens using a modified version of the Braak and Braak staging protocol for changes related to AD. The percentages of mixed LB disease and AD versus pure LB disease varied from 91% mixed and 9% pure to 34% mixed and 66% pure, depending upon which diagnostic criteria for AD were employed. Most dementia brains with LB occupied higher modified Braak stages than controls, but lower ones than pure AD specimens. A minority of the dementia brains with LB had no more AD-type pathology than controls.