Survival and plasticity of basal forebrain cholinergic systems in mice transgenic for presenilin-1 and amyloid precursor protein mutant genes

The basalo-cortical cholinergic system was characterized in mice expressing mutant human genes for presenitin-I (PSI), amyloid precursor protein (APP), and combined PS/APP. Dual immunocytochemistry for ChAT and A beta revealed swollen cholinergic processes within cortical plaques in both APP and PS/APP brains by 12 months, suggesting aberrant sprouting or redistribution of cholinergic processes in response to amyloid deposition. At 8 months, cortical and subcortical ChAT activity was normal (PS/APP) or elevated (PS, APP frontal cortex), while cholinergic cell counts (nBM/SI) and receptor binding were unchanged. ChAT mRNA was up-regulated in the nBM/SI of all three transgenic lines-at 8 months. The data indicate that the basal forebrain cholinergic system does not degenerate in mice expressing AD-related transgenes, even in mice with extreme amyloid load. The PSI or APP transgene appears to enhance the cholinergic phenotype in younger mice, but this involves aberrant sprouting and redistribution of cortical cholinergic processes. NeuroReport 12:1377-1384 (C) 2001 Lippincott Williams & Wilkins.