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P2‐240: The diabetes associated protein, SorCS1 regulates APP metabolism
Author(s) -
Lane Rachel,
Attie Alan,
Ehrlich Michelle,
Gandy Sam
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.2011.05.1123
Subject(s) - biology , transfection , effector , receptor , hek 293 cells , vacuolar protein sorting , microbiology and biotechnology , endocrinology , medicine , intracellular , biochemistry , gene , endosome
individuals (87 years and older) exhibiting AD neuropathology with and without clinical dementia. Eighteen ND-HPC and 6AD subjects were investigated by ELISAs and a battery of Western blots to determine the expression of Aß, APP, tau, a-synuclein, and a variety of other markers related to aging, inflammation and neurodegeneration. Results: Mean Braak stage values for AD and ND-HPC groups were 5.3 and 3.9, respectively although neuropathological analyses of total plaque score, cerebral amyloid angiopathy score, white matter rarefaction score and NFT score exhibited no significant differences. No obvious differences in ApoE allelic frequency were apparent between the groups. ELISA revealed that mean Aß40 levels extracted using glass-distilled formic acid/guanidine hydrochloride were significantly different, although the AD group contained 2 outliers. A11 (oligomer), IDE, PEDF, BDNF were significantly elevated in AD patients while APP, BACE, VEGF, and ApoE levels in AD were significantly decreased compared to ND-HPC.Conclusions:AD is often defined in relation to amyloid deposits, although our experiments reveal that neither plaque density nor Aß peptide levels are strongly associated with dementia. In addition, NFT pathologywas less abundant in the ND-HPC group. Other angiogenesis-associated markers such as PEDF and VEGF exhibit inverse quantitative relationships in AD patients. Decreased quantities of APP and ApoE in AD suggest impaired synthesis or enhanced turnover. Interestingly, BACE and IDE levels are decreased and elevated in AD respectively, suggesting an altered equilibrium between the synthesis and degradation of Aß. The elevated amounts of truncated proBDNF (28 kDa) in AD suggest aberrant proteolytic processing with potential consequential effects on brain homeostasis.