ACCUMULATION OF AMYLOID PRECURSOR PROTEIN IN DAMAGED NEURONAL PROCESSES AND MICROGLIA FOLLOWING INTRACEREBRAL ADMINISTRATION OF ALUMINUM SALTS

Alzheimer's disease is characterized by neurofibrillary tangles and amyloid deposits, with the latter probably occurring because of abnormal accumulation and/or processing of amyloid precursor protein (APP). Aluminum salts are known to be neurotoxic and to be capable of inducing neurofibrillary tangles. We explored the effects of intraventricular or intrastriatal injections of AlCl3 on the immunodistribution of APP in rat brain. There was a striking and long-lasting accumulation of APP in affected neurites, as well as in activated microglia/macrophages. Abnormal neurites also showed argentophilic changes, neurofilament accumulation, and Alz50 immunoreactivity. However, no extracellular amyloid fibrils were seen. The results, taken together with previous studies on colchicine, are consistent with the hypothesis that interruption of axoplasmic flow can lead to both APP accumulation and cytoskeletal changes.