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Dementia 2016
September 29-October 01, 2016
Volume 6 Issue 5(Suppl) J Alzheimers Dis Parkinsonism 2016
ISSN:2161-0460 JADP, an open access journal
conferenceseries .com
September 29-October 01, 2016 London, UK
5th International Conference on
Alzheimer’s Disease & Dementia
J Alzheimers Dis Parkinsonism 2016, 6:5(Suppl)
Genetics and Molecular Pathology Laboratory, Faculty of Medicine and Pharmacy
Nadia El Kadmiri
Hassan Ii University of Casablanca, Morocco
Neuroproteomics studies conducted in recent years have highlighted the potential involvement of the oxidoreductase,
glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in Alzheimer Disease (AD) associated proteins, including the
β-amyloid, β-amyloid precursor. In our previous study we elucidated the critical role of GAPDH and its interaction with
β-amyloid in the blood of Moroccan patients with familial AD (FAD) carrying presenilin mutations.
The aim of this current study was to assess the mechanism responsible of decreased expression of GAPDH protein in the
blood of Moroccan FAD cases. Our result revealed a non-significant difference of mRNA expression level of GAPDH from
FAD cases carrying mutations as compared to healthy controls and FAD case confirmed at autopsy (P> 0.05). Our finding is
consistent with several studies by showing the direct involvement of GAPDH in amyloid aggregation; the GAPDH in AD can
undergo many different oxidative post-translational modifications, which affects its chemical structure and biological activity.
These Data open prospects to clarify more these mechanisms in blood of AD cases by aiming to use GAPDH as a biomarker
for diagnostics and monitoring AD modification.
Clathrin endocytic pathway as new player in Amyloid beta pathway
C. Matrone, Poulsen E. Toftgaard, A. Larsen, A. Zollo, A.L. Jørgensen and J.J. Enghild
Aarhus University, Denmark
The β-amyloid precursor protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein
(Aβ) in Alzheimer’s disease (AD). However, our understanding of the normal function of APP is still patchy. Emerging
evidence indicates that a dysfunction inAPP trafficking and degradation can be responsible for neuronal deficits and progressive
degeneration in humans.
We recently reported that Y682 mutation on the 682-YENPTY-687 domain of APP, devoted to APP internalization and
trafficking (1) affects APP binding to some specific adaptors leading to an anomalous compartmentalization of APP, defects
in the autophagy machinery, progressive premature neuronal degeneration and dementia in mice (2-3). A comparative Mass
spectrometry analysis between mutated and control mice leaded to the identification of some crucial proteins that might be
probably responsible of the phenotype observed in mutated mice (2,3). Two of these proteins, named Clathrin and its adaptor,
AP2, are part of a big protein complex controlling APP trafficking inside neurons (4). Notably, the relevance of these proteins
in the APP pathway and functions was further demonstrated in neuronal progenitors from Alzheimer’s disease patients.
Overall, our results consolidate and refine the importance of APP adaptors in APP normal functions from an animal
model of premature aging/dementia and from human differentiated stem cells. Additionally, they open the perspective to
consider these adaptors as potential targets for the design and development of new therapeutic strategies.