Thiamine deficiency alters APP but not presenilin-1 immunoreactivity in vulnerable brain regions.
Presenilin-1 (PS-1) and amyloid precursor protein (APP) have been linked to the pathogenesis of Alzheimer's disease. While APP accumulation is well documented in several models of brain injury, the role of PS-1 levels in neurodegeneration, if any, remains to be elucidated. The current studies examined PS-1 and APP expression in brain following thiamine deficiency (TD), a nutritional model associated with impaired oxidation and selective neurodegeneration. TD did not alter PS-1 immunoreactivity in any region of rodent brain before or after cell loss. In contrast, APP immunoreactivity accumulated in swollen neurites within, or around lesions in rats, or in abnormal clusters in mice. Thus, alterations in APP but not PS-1 levels are involved in TD-induced neurodegeneration.
Calingasan
N Y
NY
Department of Neurology and Neuroscience, Cornell University Medical College, Burke Medical Research Institute, White Plains, NY 10605, USA.
Gandy
S E
SE
Gibson
G E
GE
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1; D051381:Rats; D011916:Rats, Inbred F344; D013832:Thiamine Deficiency / Q000378:metabolism* / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1