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P1‐400: TAU AND ALPHA‐SYNUCLEIN SELECTIVE BINDING COMPOUNDS DERIVED FROM APRINOIA THERAPEUTIC'S PM‐PBB3 BINDING‐SITE FOCUSED COMPOUND COLLECTION
Author(s) -
Tempest Paul,
Ono Maiko,
Higuchi Makogto,
Shimada Hitoshi,
Suhara Tetsuya,
Zhang Ming-Rong,
Tai Chin Yin,
Carroll Vincent,
Tamagnan Gilles,
Marek Ken,
Barret Olivier,
Alagille David,
Jang Ming-Kuei
Publication year - 2018
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.2018.06.408
Subject(s) - progressive supranuclear palsy , neuroscience , chemistry , binding site , alpha synuclein , medicine , psychology , biochemistry , pathology , parkinson's disease , disease
associations between CMBs, WMHs, and CSF levels of Ab1-42. Methods: Imaging measures of CMBs and WMHs were collected from 62 participants who also had concomitant CSF sampling. CSF levels of Ab1-42, indicating the presence or absence of ADtype amyloidosis pathology, were measured and fluid-attenuated inversion recovery (FLAIR) imaging and gradient recalled echo (GRE) were obtained to assess WMHs and CMBs. CMBs were visually rated using the well validated microbleed anatomical rating scale (MARS). Partial correlation and linear regression analyses were conducted to examine the association of lobar CMBs with CSF Ab1-42. Results: The mean age was 74.9 6 7.4 years, 45% were male and the mean years of educational attainment were 16.96 3.1 years. Partial correlation analyses showed an association between parietal lobe CMBs and lower CSF levels of Ab1-42 (rho 1⁄4 0.27, p 1⁄4 0.04). CMBs in the frontal, temporal and occipital lobes were not correlated with the CSF levels of Ab1-42. Linear regression analysis demonstrated that parietal lobe CMBs were strongly associated with lower CSF levels of Ab1-42 (p 1⁄4 0.04, beta1⁄4 0.29). Conclusions:Parietal lobe CMBs showed a strong association with lower CSFAb1-42, providing evidence that CMBs in the parietal lobe represent a potential surrogate imaging biomarker for sporadic AD in subjects who have not undergone direct amyloid assessments. Additional studies examining the association of lobar CMBs with regional WMHs and specific patterns of cognitive decline are under investigation currently.