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Title

Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease

AuthorsBlázquez-Llorca, Lidia ; García-Marín, Virginia ; Merino-Serrais, Paula ; Ávila, Jesús ; DeFelipe, Javier
KeywordsAxons
Mossy Fibers
Phosphorilation
Alzheimer´s disease
Glutamatergic terminals
Hippocampal formation
Tau protein
Thorny excrescences
Issue Date2011
PublisherIOS Press
CitationJournal of Alzheimer's Disease 26:683-698 (2011)
AbstractA key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main feature of AD is the abnormal phosphorylation of the tau protein and the presence of tangles. The sequence of cellular changes related to tau phosphorylation and tangle formation has been studied with an antibody that binds to diffuse phosphotau (AT8). Moreover, another tau antibody (PHF-1) has been used to follow the pathway of neurofibrillary (tau aggregation) degeneration in AD. We have used a variety of quantitative immunocytochemical techniques and confocal microscopy to visualize and characterize neurons labeled with AT8 and PHF-1 antibodies. We present here the rather unexpected discovery that in AD, there is conspicuous abnormal phosphorylation of the tau protein in a selective subset of dendritic spines. We identified these spines as the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state. Since thorny excrescences represent a major synaptic target of granule cell axons (mossy fibers), such aberrant phosphorylation may play an essential role in the memory impairment typical of AD patients.
Publisher version (URL)http://dx.doi.org/10.3233/JAD-2011-110659
URIhttp://hdl.handle.net/10261/57129
DOI10.3233/JAD-2011-110659
ISSN1387-2877
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