The beta-amyloid-related proteins presenilin 1 and BACE1 are axonally transported to nerve terminals in the brain.
In this study, we show that removal of entorhinal cortex (ERC) afferents to hippocampus reduces levels of presenilin 1 (PS1) in the dentate gyrus of APPswe/PS1DeltaE9 transgenic (Tg) mice. PS1 immunoreactivity on the deafferented dentate gyrus decreases by approximately 25% and 50%, 2 and 4 weeks post-lesion compared to the contralateral side; by Western blotting, there is an approximately 40% decrease of the 43 kDa (full length) PS1 and an approximately 80% decrease of the 28 kDa (N-terminal fragment) PS1 on the lesioned dentate gyrus. Levels of beta-site APP Cleavage Enzyme 1 (BACE1) immunoreactivity also decrease by approximately 50% and 65% 2 and 4 weeks post-lesion. Together, these data demonstrate that PS1 and BACE1 are transported from the entorhinal cortex to the hippocampus via axons of the perforant pathway.
Sheng
Jin G
JG
Division of Neuropathology and the Alzheimer's Disease Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Price
Donald L
DL
Koliatsos
Vassilis E
VE
D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001370:Axonal Transport / Q000502:physiology*; D019771:Axotomy; D015153:Blotting, Western; D001921:Brain / Q000502:physiology*; D004525:Efferent Pathways / Q000502:physiology; D010450:Endopeptidases; D018728:Entorhinal Cortex / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019580:Perforant Pathway / Q000502:physiology*; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse