title: Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections.
abstract: A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs.
authors.affiliation: Laboratory of Radiation Safety, National Center for Geriatrics and Gerontology (NCGG), 7-430, Morioka-cho, Obu, Aichi 474-8511, Japan. yoshimit@ncgg.go.jp.
authors.forename: T
authors.initials: T
authors.lastname: Yoshimi
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: S
authors.initials: S
authors.lastname: Taira
authors.forename: A
authors.initials: A
authors.lastname: Okuno
authors.forename: R
authors.initials: R
authors.lastname: Mikawa
authors.forename: S
authors.initials: S
authors.lastname: Murayama
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: O
authors.initials: O
authors.lastname: Takikawa
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000906:Antibodies / Q000737:chemistry; D015415:Biomarkers / Q000737:chemistry; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015925:Cryopreservation; D004867:Equipment Design; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007477:Ions; D013058:Mass Spectrometry / Q000379:methods*; D010100:Oxygen / Q000737:chemistry; D010766:Phosphorylation; D012371:Robotics; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods*; D016875:tau Proteins / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D015415:Biomarkers; D007477:Ions; D016875:tau Proteins; D010100:Oxygen