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S4‐01‐01: Lessons from multicenter studies on CSF biomarkers for Alzheimer's disease
Author(s) -
Blennow Kaj
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1942
Subject(s) - biomarker , medicine , disease , dementia , oncology , diagnostic accuracy , diagnostic biomarker , clinical trial , cerebrospinal fluid , pathology , biology , biochemistry
ogy in AD. Taupathology is also encountered in other neurodegenerative disorders. Our laboratory showed that depending on the neurological disorder considered, different sets of Tau protein isoforms were aggregated. For instance, the six Tau isoforms aggregate in AD whereas only three isoforms aggregate in Pick bodies of Pick’s Disease. These observations suppose that subsets of Tau isoforms are expressed in sub neuronal populations, or alternatively, a defective splicing of Tau is an early event of neurodegeneration. Propagation of Tau pathology may also be specific to these different Tauisoforms. The use of animal models will be a key asset for understanding Taupathology. Using the Thy-Tau22 mouse transgenic line developed in our laboratory, analysis of the kinetics of Tauphosphorylation, aggregation and neuronal death in parallel to electrophysiological and behavioural parameters indicates a dys-connection between cognition deficits and neuronal cell death. This model exhibits progressive neuron-specific AD-like Tau pathology devoid of any motor deficits. A progressive development of Taupathology is observed in the hippocampus and amygdala, which parallels behavioural impairments as well as electrophysiological alterations. These latter changes are observed despite of any striking loss of neuronal/ synaptic markers until 12 months of age in the hippocampus. In addition, in the hippocampus, hyperand abnormally phosphorylated Tau species accumulate within the somato-dendriticarea, supporting a possible influence on hippocampal-dependent plasticity always confirmed by behavioural and electrophysiological evaluations. Conclusions: In conclusion, AD and other Tauopathies have likely different etioliges. They are characterized by differenct Tau aggregates, which may spread in different ways and explain their different clinical presentations. Animal models of Tau pathology may mimie part of the pathology (phosphorylation and/or aggregation, propagation vs. diffusion) and help for the development of new, innovative therapeutic strategies.