Premium
[IC‐P‐193]: FMRI OF VISUAL STIMULI IN A TAU MODEL OF ALZHEIMER's DISEASE
Author(s) -
Nahavandi Payam,
Niranjan Arun,
Ohene Yolanda,
Harrison Ian F.,
Ismail Ozama,
Murray Tracey K.,
Johnson Ross A.,
O'Neill Michael J.,
Collins Emily C.,
Lythgoe Mark F.,
Wells Jack A.
Publication year - 2017
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.2017.06.2568
Subject(s) - tauopathy , neuroscience , functional magnetic resonance imaging , psychology , neuroimaging , audiology , neurodegeneration , medicine , disease , pathology
amyloid binders. Binding to AD and non-AD brain tissue was performed using autoradiography (ARG) on human brain sections. The specific binding was compared to the corresponding signals on brain tissues of non-demented control subjects. The pharmacokinetic profiles of F-PI-2620 were evaluated in mice and non-human primates. Results:PI-2620 displayed a high affinity for Tau in AD brain homogenate competition-assays (IC50: 1.8 nM). In addition to its high affinity binding to Tau, the compound showed excellent selectivity with no detectable off-target binding to betaamyloid orMAOA/B. Specific binding to Tau deposits was demonstrated by ARG on AD brain sections (Braak I-VI), Pick’s and PSP pathology indicating detection of both 3R and 4R Tau deposits. No specific tracer binding was detected on brain slices from nondemented donors. Good brain uptake and fast wash-out was observed in healthy mice and non-human primates. Conclusions: PI-2620 demonstrated improved characteristics in preclinical models with high affinity, good selectivity and excellent preclinical PK properties. The compound is currently being evaluated in clinical studies.