Early Tau pathology involving the septo-hippocampal pathway in a Tau transgenic model: relevance to Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary tangles. Cholinergic dysfunction is also a main pathological feature of the disease. Nevertheless, the links between cholinergic dysfunction and neuropathological hallmarks of Alzheimer's are still unknown. In the present study, we aimed to further investigate Tau aggregation in cholinergic systems, in a Tau transgenic mouse model. THY-Tau22 mice have recently been described as a novel model of Alzheimer-like Tau pathology without motor deficits. This strain presents an age-dependent development of Tau pathology leading to synaptic dysfunctions as well as learning and memory impairments. In the present work, we observed that Tau pathology differentially affects cerebral structures. Interestingly, early Tau pathology was observed in both hippocampus and basal forebrain. Moreover, some morphological as well as functional alterations of the septohippocampal pathway suggest a disconnection between these two key brain regions in Alzheimer's disease. Finally, these data suggest that Tau pathology may participate in cholinergic degeneration.
Belarbi
Karim
K
Inserm, U837, Lille, France. luc.buee@inserm.fr.
Schindowski
Katharina
K
Burnouf
Sylvie
S
Caillierez
Raphaëlle
R
Grosjean
Marie-Eve
ME
Demeyer
Dominique
D
Hamdane
Malika
M
Sergeant
Nicolas
N
Blum
David
D
Buée
Luc
L
D000367:Age Factors; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D005998:Glycine / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009434:Neural Pathways / Q000473:pathology; D011392:Proline / Q000235:genetics; D020665:Septum of Brain / Q000473:pathology*; D012694:Serine / Q000235:genetics; D013266:Stilbamidines / Q000378:metabolism; D014633:Valine / Q000235:genetics; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C054369:MAPT protein, human; D013266:Stilbamidines; D016875:tau Proteins; D012694:Serine; D011392:Proline; D014633:Valine; D005998:Glycine