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P3‐193: Distinct tau aggregation form involved in synapse loss and neuron loss
Author(s) -
Takashima Akihiko
Publication year - 2009
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.2009.04.1067
Subject(s) - synapse , neurodegeneration , tau protein , tauopathy , chemistry , neuron , neuroscience , microbiology and biotechnology , biology , alzheimer's disease , pathology , medicine , disease
the degree of downregulation correlates closely with disease progression, suggesting that decreased BDNF may be an underlying cause of memory impairment. The human BDNF gene produces multiple differentially regulated transcripts; our previous research demonstrated that transcripts I, II, IV and VI are downreguated in Alzheimer’s disease, and that aggregated beta-amyloid specifically mediates downregulation of BDNF transcripts IV and VI. Objectives: In this study we tested whether tau pathology is associated with decreased BDNF mRNA, and if so, which transcripts are affected. Methods: To study the effects of tau pathology in vivo, we obtained human post mortem tissue from subjects with non-Alzheimer’s tauopathies, diseases that exhibit pathological alterations in tau without beta-amyloid pathology, from Dr. VMY Lee (University of Pennsylvania, USA). We assayed BDNF mRNA levels in cortical tissue of controls (n1⁄412) and subjects with Pick’s disease (n1⁄48), corticobasal degeneration (n1⁄412), and progressive supranuclear palsy (n1⁄413), using quantitative real-time RT-PCR. Results: We demonstrated a significant downregulation of BDNF in Pick’s disease (p1⁄40.012) and a trend towards downregulation in corticobasal degeneration (p1⁄40.066) compared to controls, implicating tau modifications in BDNF downregulation. In Pick’s disease and corticobasal degeneration we found that BDNF transcripts I, II, IV and VI were decreased compared to controls, but between-group differences were not statistically significant. Conclusions: BDNF mRNA is significantly downregulated in Pick’s disease, a condition exhibiting similar tau modifications to those in Alzheimer’s disease. The transcripts that are decreased in tauopathy cortical tissue are the same transcripts that are significantly downregulated in Alzheimer’s disease cortex. Because aggregated beta-amyloid downregulates only transcripts IV and VI whereas tau affects transcripts I, II, IV and VI, tau may affect BDNF transcript levels via different mechanisms than beta-amyloid.