Journal
CURRENT ALZHEIMER RESEARCH
Volume 8, Issue 6, Pages 633-638Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156720511796717230
Keywords
Alzheimer's disease; Cholinergic neurons; Nerve growth factor; Tau; Transgenic model
Categories
Funding
- Inserm
- CNRS
- IMPRT
- University Lille 2
- Lille County Hospital (CHR-Lille)
- Region Nord/Pas-de-Calais
- FEDER
- ADERMA
- DN2M
- Deutsche Forschungsgemeinschaft [DFG - ZI 1143/1-1]
- France Alzheimer
- Federation pour la Recherche sur le Cerveau
- LECMA
- European Community: MEMOSAD [200611]
- Consejeria de Educacion of JCCM
- Canadian Institutes of Health Research (CIHR)
- [ANR-08-MNPS-002/AMYTOXTAU]
- [ANR-JC07-184902/ADONTAGE]
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Alzheimer's 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.
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