Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Loss of Medial Septum Cholinergic Neurons in THY-Tau22 Mouse Model: What Links with tau Pathology?

Author(s): K. Belarbi, S. Burnouf, F.-J. Fernandez-Gomez, J. Desmercieres, L. Troquier, J. Brouillette, L. Tsambou, M.-E. Grosjean, R. Caillierez, D. Demeyer, M. Hamdane, K. Schindowski, D. Blum and L. Buee

Volume 8, Issue 6, 2011

Page: [633 - 638] Pages: 6

DOI: 10.2174/156720511796717230

Price: $65

Abstract

Alzheimers disease (AD) is a neurodegenerative disorder histologically defined by the cerebral accumulation of amyloid deposits and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Loss of basal forebrain cholinergic neurons is another hallmark of the disease thought to contribute to the cognitive dysfunctions. To this date, the mechanisms underlying cholinergic neurons degeneration remain uncertain. The present study aimed to investigate the relationship between neurofibrillary degeneration and cholinergic defects in AD using THY-Tau22 transgenic mouse model exhibiting a major hippocampal AD-like tau pathology and hyperphosphorylated tau species in the septohippocampal pathway. Here, we report that at a time THY-Tau22 mice display strong reference memory alterations, the retrograde transport of fluorogold through the septohippocampal pathway is altered. This impairment is associated with a significant reduction in the number of choline acetyltransferase (ChAT)-immunopositive cholinergic neurons in the medial septum. Analysis of nerve growth factor (NGF) levels supports an accumulation of the mature neurotrophin in the hippocampus of THY-Tau22 mice, consistent with a decrease of its uptake or retrograde transport by cholinergic terminals. Finally, our data strongly support that tau pathology could be instrumental in the cholinergic neuronal loss observed in AD.

Keywords: Alzheimer's disease, Cholinergic neurons, Nerve growth factor, Tau, Transgenic model, cognitive impairments, dementia, neurofibrillary tangles, sequential cleavage, neurotrophins, discrepancies, forebrain cholinergic neurons, cognitive dysfunction, P75NTR receptor


Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy