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P2‐002: In‐vivo detection of age‐related cerebral glucose uptake alterations by pet in microcebus murinus primates
Author(s) -
Daorieux Ole ne,
JosephMathurin Nelly,
Chaigneau Marion,
Guillermier Martine,
Houitte Diane,
Josephine Charlene,
David Santin Mathieu,
Kraska Audrey,
VanCamp Nadja,
Phillippe Hantraye,
Metzker Friedrich,
Perret Martine,
Dhenain Marc
Publication year - 2011
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.2011.05.2437
Subject(s) - atrophy , medicine , cerebellum , cohort , neuroimaging , pathology , neuroscience , nuclear medicine , psychology
Background:Due to increasing numbers of patients suffering fromAlzheimer’s Disease (AD) and no effective therapies so far, there is an exigent need for a reliableand inexpensive diagnosis at anearly stageof the disease.Aggregates of amyloid ß and tau protein are the physiological markers of the disease. Therefore inhibition and reversal of this protein-aggregation are subjects of clinical studies. The established PET tracer PIB is so far limited to exclude the AD diagnosis. The outcome of clinical studies can be monitored by the combination of cognitive ability assays and the sampling of biomarkers from cerebrospinal fluid, which is supported by PIB PET imaging. A distinct AD diagnosis is possible postmortem only via the histological examination of brain tissue. Neither of these approaches is suitable for a large cohort survey. Moreover, community physicians fail to diagnose up to 33% ofmild dementia cases. Novel markers are required to establish a reliable, early diagnosis of a pathological accumulation of tau andAß in the living patient. Established radio diagnostic probes allowmonitoring individual disease progress but display restricted ability to differentiate AD patients from healthy controls. Hence an important criterion for the development of novel imaging techniques and probes is their ability to differentiate clearly tau-protein depositions from Aßaggregates. ThereforewedevelopbrainMethods:Thereforewedeveloped brain penetrating, selective fluorescent probes for the in vivo detection of tauPHFandAß-aggregates inADpatients and animalmodels.Results: Iterative cycles of ligand design, synthesis and histology of human AD tissue resulted in the identification of bright-fluorescent binders for amyloid plaques and tauPHF. Conclusions: A biomarker-supported diagnosis is of essential importance for future therapies of ADs both for clinical studies and for awidespread screening of high-risk groups with respect to an early beginning of therapy.