Study for novel biomarkers for Alzheimer's disease

To facilitate early diagnosis of AD dementia and other non-AD dementias, simple and quick assay of CSF and plasma biomarkers for Alzheimer disease and non-AD dementia were studied and developed. 1) To identify presence of plasma tau and p-tau, anti-human CNS tau antibodies (tauA/tauB) were developed. Western blot analysis of immunoprecipitated samples from CSF and plasma of TgtauP301L mice using tauA/tauB revealed the real presence of metabolized tau fragments from CNS and PNS. Further confirmation of the presence of CNS tau was necessary. Basic evaluation of CSF and plasma α-synuclein showed adequate reproducibility and sensitivity. Measurements of 105 cases of AD and non-AD dementias showed that increased levels of MCI, and other neurological diseases CSF As40，As42, tauおよび血液As40，As42測定値in AD, MCI, and controls, but, decreased levels of α-synuclein in Parkinson diseases. The levels of CSF As40, As42, tau andplasma As40，As42were correlated with those levels of α-synuclein. High sensitive ELISA of TDP-43 are developing. Candidate 28 molecules as Alzheimer disease identified by proteomics analysis of CSF proteins with more than 30,000 kD were further evaluated using bioinformatics data base for patent filing.

To facilitate early diagnosis of AD dementia and other non-AD dementias, simple and quick assay of CSF and plasma biomarkers for Alzheimer disease and non-AD dementia were studied and developed. 1) To identify presence of plasma tau and p-tau, anti-human CNS tau antibodies (tauA/tauB) were developed. Western blot analysis of immunoprecipitated samples from CSF and plasma of TgtauP301L mice using tauA/tauB revealed the real presence of metabolized tau fragments from CNS and PNS. Further confirmation of the presence of CNS tau was necessary. Basic evaluation of CSF and plasma α-synuclein showed adequate reproducibility and sensitivity. Measurements of 105 cases of AD and non-AD dementias showed that increased levels of MCI, and other neurological diseases CSF As40，As42, tauおよび血液As40，As42測定値in AD, MCI, and controls, but, decreased levels of α-synuclein in Parkinson diseases. The levels of CSF As40, As42, tau andplasma As40，As42were correlated with those levels of α-synuclein. High sensitive ELISA of TDP-43 are developing. Candidate 28 molecules as Alzheimer disease identified by proteomics analysis of CSF proteins with more than 30,000 kD were further evaluated using bioinformatics data base for patent filing.