Molecular and Chemical Neuropathology

, Volume 31, Issue 2, pp 171–186

Effects of acidosis on the distribution and processing of the β-amyloid precursor protein in cultured hippocampal neurons

Original Articles

DOI: 10.1007/BF02815241

Cite this article as:
Brewer, G.J. Molecular and Chemical Neuropathology (1997) 31: 171. doi:10.1007/BF02815241


Reported increases in brain lactate production in Alzheimer disease led us to test the hypothesis that lactic acid acidosis alters the processing of the β-amyloid precursor protein, βPP, in neurons. To test this proposition, embryonic rat hippocampal neurons were first cultured for 4 d in serum-free B27/neurobasal medium. Lactic acid at 0.5 and 1 mg/mL (pH 7.1 and, 6.9, respectively) caused a dosedependent increase in cellular β-amyloid immunoreactivity detected with antibody 4G8. Acidosis did not affect secretion of βPP or its derivatives into the medium. The cytoplasmic production of βPP was slightly reduced by acidosis without a differential effect on maturation or proteolytic processing. In the substrate-bound material, which was insoluble in nonionic detergent, acidosis caused increases in an N-terminal 75-kDa band, a C-terminal 72-kDa band, and potentially amyloidogenic bands at 35 and 38 kDa. Processing to the 4-kDa amyloid β protein was not observed in these nearly pure rat neuronal cultures. These results suggest that mild acidosis is sufficient to alter neuronal processing of the amyloid precursor protein into potentially amyloidogenic forms and increase certain βPP fragments bound to the substrate. If a similar process occurs in the presence of other cell types in the aging brain, acidosis may stimulate an extracellular deposition of amyloid and contribute to the pathogenesis of Alzheimer disease.

Index Entries

Neuron culture acidosis β-amyloid hippocampus Alzheimer disease 

Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  1. 1.Department of Medical Microbiology and ImmunologySouthern Illinois University School of MedicineSpringfield

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